MedWorm: Eloxatin

  5. A novel biomarker of axonal dysfunction in oxaliplatin-induced neurotoxicity

Introduction: Oxaliplatin, a platinum-based chemotherapy utilised in the treatment of colorectal cancer, produces prominent dose-limiting neurotoxicity. Acute neurotoxicity develops immediately following infusion and resolves within days, while chronic neuropathy develops with higher cumulative doses. (Source: Clinical Neurophysiology)

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  Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer.

Authors: Guiu B, Vincent J, Guiu S, Ladoire S, Ortega-Deballon P, Cercueil JP, Chauffert B, Ghiringhelli F Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease, resulting in increased local drug concentrations. Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy. The patient was treated with a combination of gemcitabine and oxaliplatin using HAI. The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI. The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper...

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  Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

Conclusion: These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo. (Source: BioMed Central)

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  Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site

Despite the widespread use of oxaliplatin-based regimens for colorectal and other gastrointestinal cancers, there is surprisingly little information regarding their empiric use for the treatment of carcinoma of unknown primary site (CUP). In the current study, the combination of oxaliplatin and capecitabine in patients with recurrent and refractory CUP was examined.Patients with CUP who had received at least 1 previous chemotherapy regimen were treated with oxaliplatin (130 mg/m2 intravenously on Day 1) and capecitabine (1000 mg/m2 orally twice daily on Days 1-14). Treatment cycles were repeated every 21 days. Patients with objective response or stable disease after 2 cycles continued treatment for 6 cycles or until disease progression.Nine of 48 patients (19%) had objective responses to t...

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  Hyperthermic intraperitoneal chemotherapy with oxaliplatin and without adjuvant chemotherapy in stage IIIC ovarian cancer.

ConclusionHIPEC without adjuvant chemotherapy is both feasible and safe, but with a high rate of grade 3-5 toxicity. Survival results are encouraging but should be confirmed in a randomized trial. PMID: 20202920 [PubMed - as supplied by publisher] (Source: Bulletin du Cancer)

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  Out-of-pocket payment and cost-effectiveness of XELOX and XELOX plus bevacizumab therapy: from the perspective of metastatic colorectal cancer patients in Japan

Conclusions  We clarified the out-of-pocket payment and cost-effectiveness of chemotherapy of MCRC patients in Japan. Our previous survey shows it is highly possible that many patients prefer to pay that incremental out-of-pocket payment to gain one additional QAPFS year. However, our cost-effectiveness analysis was not conducted from the perspective of society or healthcare payers. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10147-010-0045-xAuthors Takeru Shiroiwa, The University of Tokyo Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences Yakugaku-toshokan 4F, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033 JapanTakashi Fukuda, The University of Tokyo Department of Health Economics and Epidemiology Research, School of Pu...

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  Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer

We reported previously (Jan. 3, 2008, issue)1 that capecitabine and oxaliplatin are as effective as infused fluorouracil ... (Source: New England Journal of Medicine)

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  Neoadjuvant chemotherapy with oxaliplatin of no benefit in locally advanced rectal cancer: Results of the Phase III Trial ACCORD 12/0405-Prodige 2

Source: JCO Area: News According to research published early online in the Journal of Clinical Oncology oxaliplatin shows no benefit when used as part of a neoadjuvant chemotherapy regimen in patients with locally advanced rectal cancer, and therefore should not be used.   Because neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer, researchers evaluated neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin.   Patients were randomised to receive 5 weeks of treatment with radiotherapy with concurrent capecitabine 800 mg/m2 twice daily 5 days per week (Cap 45; n=299) or radiotherapy with capecitabine 800 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m2 once weekly (Cap...

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  [Reflection and Reaction] Neoadjuvant chemotherapy in MRI-staged rectal cancer

In today's The Lancet Oncology, Chua and colleagues describe a new treatment schedule in MRI-defined locally advanced rectal cancer, with 12 weeks of neoadjuvant capecitabine and oxaliplatin followed by chemoradiation with concurrent capecitabine, to a total dose of 54 Gy. Patients then underwent total mesorectal excision after a defined interval. Overall, 20% of the intention-to-treat population achieved a pathological complete response (pCR). Unusually, long-term results are provided for this phase 2 study, with a median follow-up of 55 months. 3-year and 5-year progression-free survival in the intention-to-treat population of 68% and 64%, respectively, is impressive for this group of patients, as is the 5-year overall survival of 75%. The authors imply that this excellent outcome is ass...

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  [Articles] Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial

Patients with poor-risk rectal cancer defined by MRI can be at high risk of disease recurrence despite standard chemoradiotherapy and optimum surgery. We aimed to assess the safety and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision, a treatment strategy developed to enhance the outcome of this population. (Source: The Lancet Oncology)

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  Comparison of Patient Outcomes According to Histology Among Pemetrexed-Treated Patients With Stage IIIB/IV Non-Small-Cell Lung Cancer in Two Phase II Trials.

Conclusion: In patients treated with pemetrexed/ platinum doublets, nonsquamous histology was associated with better outcomes. The benefit of pemetrexed treatment among patients with nonsquamous histology is consistent with the results reported from previous studies. PMID: 20199979 [PubMed - in process] (Source: Clinical Lung Cancer)

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  Erratum to: Severe respiratory symptoms to oxaliplatin infusion: a case report of delayed hypersensitivity reaction

Content Type Journal ArticleCategory ErratumDOI 10.1007/s10637-010-9404-8Authors Simona Potenza, Second University of Naples Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine Via Costantinopoli 16 80138 Naples ItalyGuglielmo Nasti, National Cancer Institute of Naples Colorectal Department, ‘G. Pascale’ Foundation Via M. Semmola 80131 Naples ItalyAlessandro Ottaiano, National Cancer Institute of Naples Colorectal Department, ‘G. Pascale’ Foundation Via M. Semmola 80131 Naples ItalyAmelia Filippelli, Second University of Naples Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine Via Costantinopoli 16 80138 Naples ItalyFrancesco Rossi, Second University of Naples Section of Pharmacology “L. Donatelli”, Department of Exp...

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  TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer

Authors: M F Ziauddin, Z S Guo, M E O'Malley, F Austin, P J Popovic, M A Kavanagh, J Li, M Sathaiah, P Thirunavukarasu, B Fang, Y J Lee & D L Bartlett (Source: Gene Therapy)

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  European CHMP issues positive opinion on extending licence of capecitabine (Xeloda®) to include adjuvant treatment of stage III colon cancer

Source: PharmacyEurope, Roche Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has adopted a positive opinion on extending the licence of capecitabine (Xeloda®) to include the adjuvant treatment of stage III colon cancer in combination with oxaliplatin. (Source: NeLM - News)

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  European Medicines Agency grants positive opinion for Xeloda in combination with oxaliplatin for the adjuvant treatment of early colon cancer

Roche announced today that Xeloda (capecitabine) in combination with oxaliplatin (a combination known as XELOX) has been recommended by the Committee on Human Medicinal Products (CHMP) for the adjuvant (post-surgery) treatment of patients with early colon cancer. The CHMP positive recommendation was based on results from the phase III pivotal NO16968 (XELOXA) study, one of the largest studies of patients with stage III (early) colon cancer, which showed that patients taking XELOX immediately after surgery lived disease-free for longer compared to those treated with the chemotherapy regimen 5-fluorouracil/leucovorin (5-FU/LV). (Source: Roche Investor Update)

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  Cetuximab and chemoradiation for rectal cancer-is the water getting muddy?

Conclusion. Cetuximab combined with fluoropyrimidine-based chemoradiation is not currently recommended. A better understanding of the mechanisms involved in combinations of chemotherapy and radiotherapy might allow more effective future scheduling of biological and chemical agents in combination with radiation. PMID: 20180626 [PubMed - as supplied by publisher] (Source: Acta Oncologica)

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  Bevacizumab Improves Pathological Response of Colorectal Cancer Liver Metastases Treated with XELOX/FOLFOX

Conclusions  Classifying histological response based on tumor regression grades qualifies to predict the outcome of patients with colorectal cancer liver metastases. Tumor regression grading provides a standardized pathological response evaluation, against which radiologic response on chemotherapy including biologicals can be prospectively evaluated. Content Type Journal ArticleCategory Colorectal CancerDOI 10.1245/s10434-010-0972-9Authors Markus Klinger, Medical University of Vienna Department of General Surgery, Hepatobiliary Service Vienna AustriaDietmar Tamandl, Medical University of Vienna Department of General Surgery, Hepatobiliary Service Vienna AustriaSandra Eipeldauer, Medical University of Vienna Clinical Institute of Pathology Vienna AustriaStefan Hacker,...

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  Integrin beta-3 L33P: a new insight into the pathogenesis of chronic oxaliplatin-induced peripheral neuropathy?

Conclusion: The ITGB3 L33P seems to be unrelated to the development of OXLIPN, but it appears to be related to its severity. (Source: European Journal of Neurology)

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  EGF61A>G polymorphism as predictive marker of clinical outcome to first-line capecitabine and oxaliplatin in metastatic colorectal cancer

Conclusion: Polymorphism analysis of a simple blood sample is a feasible approach to biomarker analysis and the EGF61A>G polymorphism may influence the effect of first-line XELOX. Consequently, this marker deserves further investigation. (Source: Annals of Oncology)

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  Resistance to platinum-based chemotherapy in lung cancer cell lines

Conclusion  Thus, sensitivity to cisplatin appeared to be associated with DDH levels in epithelial lung cancer cell lines with the DDH-1 isoform producing the greatest effect. Results in keeping with transfection experiments with ovarian and other cell lines. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-010-1268-2Authors Jianli Chen, The Feinstein Institute for Medical Research North Shore-Long Island Jewish Health System 350 Community Drive Manhasset NY 11030 USANashwa Emara, Temple University School of Medicine Department of Pathology and Laboratory Medicine Philadelphia PA USACharalambos Solomides, Temple University School of Medicine Department of Pathology and Laboratory Medicine Philadelphia PA USAHemant Parekh, Temple University School...

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  Ultra-fast HPLC-ICP-MS analysis of oxaliplatin in patient urine.

Authors: Koellensperger G, Hann S A novel method for rapid HPLC-ICP-MS analysis of oxaliplatin in human urine was developed implementing a stationary HPLC phase with a particle size of 1.8 microm. The method allowed a cycle time of <1 min at a HPLC flow rate of 0.9 mL min(-1). Procedural limits of detection of 0.05 microg L(-1) oxaliplatin (150 fg on column) were obtained. Analysis of oxaliplatin in patient urine showed that accurate quantification of the intact drug demanded for storage at -80 degrees C and rapid measurement after thawing. PMID: 20165835 [PubMed - as supplied by publisher] (Source: Analytical and Bioanalytical Chemistry)

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  [Hepatotoxicity of metastatic colorectal cancer chemotherapy: systematic review.]

ConclusionThe fact that irinotecan may be linked to an increased risk of hepatic failure and postoperative death, which is not the case of oxaliplatine, must be took in consideration in the choice of the preoperative chemotherapy before resection of hepatic metastasis of colorectal cancer. PMID: 20167564 [PubMed - as supplied by publisher] (Source: Bulletin du Cancer)

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  What Else in Gemcitabine-Pretreated Advanced Pancreatic Cancer? An Update of Second Line Therapies.

Authors: Petrelli F, Borgonovo K, Ghilardi M, Cabiddu M, Barni S Advanced pancreatic cancer is usually treated with first-line gemcitabine (GEM) (alone or in combination). More recently, GEM has become an established part of an adjuvant therapy based on two recently-reported randomized trials. There remains unresolved the problem of second-line therapy in patients relapsed during or after adjuvant or first-line GEM-based treatment. As of today, platinum analogues in combination with fluoropyrimidine or with GEM represent the most common schedule in clinical practice with data from single-centre or multicentric phase II studies. In 2008, for the first time, a randomized phase III trial conducted on good performance status GEM-refractory patients (CONKO 003) confirmed their benefit in pr...

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  Irinotecan associated with cetuximab given every 2 weeks versus cetuximab weekly in metastatic colorectal cancer

Conclusion&lt;/b&gt; : There is no major difference of efficacy and safety between cetuximab given every 2 weeks and a weekly dosing regimen, in association with irinotecan. (Source: Journal of Cancer Research and Therapeutics)

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  A meta-analysis of chemotherapy regimen Fluorouracil/Leucovorin/Oxaliplatin Compared with Fluorouracil/Leucovorin in treating advanced colorectal cancer

Abstract: Background: We performed a meta-analysis to evaluate the efficacy and safety of Fluorouracil (FU)/Leucovorin (LV)/Oxaliplatin compared to FU/LV in treating advanced colorectal cancer.Methods: Two independent researchers identified and extracted all relevant literature using MEDLINE and the Cochrane Library Database. The regimens included arm A (FU/LV) and arm B (FU/LV/Oxaliplatin) with no other chemotherapy agent.Results: Five randomized controlled trials (RCTs) fulfilled the requirements. All RCTs showed superiority of FU/LV/Oxaliplatin to FU/LV when measuring RR (response rate) and PFS (progression-free survival); no significant improvement in OS (overall survival) was observed. This meta-analysis shows a better RR for the FU/LV/Oxaliplatin group (OR 4.02, 95% CI 2.37–6.82, p...

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  TAp73 is one of the responsible genes for the lack of response to chemotherapy depending on B-Raf mutational status.

Conclusions: Here, for the first time we report, that there is a signaling loop between B-Raf activation and p73 function.Low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab. (Source: BioMed Central)

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  Which Method to Deliver Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin? An Experimental Comparison of Open and Closed Techniques

Conclusions  Intraperitoneal hyperthermia can be achieved with both techniques. The open technique had far higher systemic absorption and abdominal tissue penetration of oxaliplatin than the closed technique. Content Type Journal ArticleCategory Translational Research and BiomarkersDOI 10.1245/s10434-010-0937-zAuthors Pablo Ortega-Deballon, University of Burgundy INSERM UMR 866, Equipe Avenir Burgundy FranceOlivier Facy, University of Burgundy INSERM UMR 866, Equipe Avenir Burgundy FranceSophie Jambet, University of Burgundy INSERM UMR 866, Equipe Avenir Burgundy FranceGuy Magnin, University Hospital Department of Anesthesiology Dijon FranceEddy Cotte, University Hospital of Lyon South Department of Surgical Oncology Pierre Bénite FranceJean L. Beltramo, School of Phar...

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  Alternating Systemic and Hepatic Artery Infusion Therapy for Resected Liver Metastases From Colorectal Cancer: A North Central Cancer Treatment Group (NCCTG)/ National Surgical Adjuvant Breast and Bowel Project (NSABP) Phase II Intergroup Trial, N9945/CI-66 [Gastrointestinal Cancer]

Conclusion Alternating HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end point of higher than 85% survival at 2 years and was clinically tolerable. However, the merits of this approach need to be established with a phase III trial. (Source: Journal of Clinical Oncology)

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  Phase II, Randomized Study of Concomitant Chemoradiotherapy Followed by Surgery and Adjuvant Capecitabine Plus Oxaliplatin (CAPOX) Compared With Induction CAPOX Followed by Concomitant Chemoradiotherapy and Surgery in Magnetic Resonance Imaging-Defined, Locally Advanced Rectal Cancer: Grupo Cancer de Recto 3 Study [Gastrointestinal Cancer]

Conclusion Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted. (Source: Journal of Clinical Oncology)

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  Cetuximab in combination therapy: from bench to clinic

Abstract  Cetuximab, a chimeric IgG1 monoclonal antibody directed against the ligand-binding domain of the epidermal growth factor receptor, offers a paradigm for the combination of molecularly targeted therapies with cytotoxic agents. In preclinical models, the addition of cetuximab to chemotherapy or radiation therapy enhances antitumor activity. Proposed mechanisms include reducing tumor cell proliferation, angiogenesis, and DNA repair capacity; increasing apoptosis; and inducing cell cycle arrest at treatment-sensitive points. These effects may enhance and restore tumor sensitivity to cytotoxic therapies. In clinical trials, the addition of cetuximab to chemotherapy improves outcomes of patients who had previously failed such agents, as illustrated in irinotecan-resistan...

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  Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: A pooled analysis of eight consecutive North Central Cancer Treatment Group (NCCTG) trials.

Authors: Jatoi A, Foster NR, Egner JR, Burch PA, Stella PJ, Rubin J, Dakhil SR, Sargent DJ, Murphy BR, Alberts SR Whether elderly patients with metastatic esophageal, gastroesophageal, and gastric cancer do as well with chemotherapy as their younger counterparts was investigated in this pooled analysis. In total, 367 patients from 8 consecutive, first-line trials were included: i) etoposide + cisplatin; ii) 5-fluorourucil + leucovorin; iii) 5-fluorouracil + levamisole; iv) irinotecan; v) docetaxel + irinotecan; vi) oxaliplatin + capecitabine; vii) docetaxel + capecitabine; and viii) bortezomib + paclitaxel + carboplatin. One hundred and fifty-four (42%) patients were >/=65 years old (range: 65-86), and 213 younger (range: 20-64). Elderly patients had worse performance scores (2-3): ...

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  Vinorelbine plus Oxaliplatin versus Vinorelbine plus Cisplatin for Advanced Non-small Cell Lung Cancer: A Systematic Review

Conclusion The clinical efficacy of NO and NP for advanced NSCLC was similar, but the side effects were different. The toxicity of NO has the tendency to be more tolerable. (Source: Chinese Journal of Lung Cancer)

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  A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens

Conclusions AZD6244 showed similar efficacy to capecitabine in terms of the number of patients with a disease progression event and of progression-free survival. AZD6244 is currently undergoing evaluation in Phase II trials in combination with other chemotherapeutic agents. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-010-9392-8Authors Jaafar Bennouna, Centre Rene Gauducheau Medical Oncology Branch Bd J. Monod 44805 Saint Herblain FranceIstvan Lang, National Institute of Oncology Budapest HungaryManuel Valladares-Ayerbes, Hospital Universitario La Coruna SpainKatalin Boer, St. John Hospital, site of St. Margit Budapest HungaryAntoine Adenis, Centre Oscar Lambret Lille FrancePilar Escudero, Hospital Clinico Lozano Blesa Zaragoza SpainTae-You Kim, National U...

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  Tumor Cell Death and ATP Release Prime Dendritic Cells and Efficient Anticancer Immunity

By destroying tumor cells, conventional anticancer therapies may stimulate the host immune system to eliminate residual disease. Anthracyclines, oxaliplatin, and ionizing irradiation activate a type of tumor cell death that elicits efficient anticancer immune responses depending on interferon (IFN) and the IFN receptor. Thus, dying tumor cells emit danger signals that are perceived by dendritic cells (DC), which link innate and cognate immune responses. Recently, we observed that ATP was released by tumor cells succumbing to chemotherapy. ATP activates purinergic P2RX7 receptors on DC, thus activating the NLRP3/ASC/caspase-1 inflammasome and driving the secretion of interleukin-1β (IL-1β). IL-1β then is required for the adequate polarization of IFN-producing CD8+ T cells. Th...

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  Adjuvant Chemotherapy for Resected Stage II and III Colon Cancer: Comparison of Two Widely Used Prognostic Calculators

Two Web-based prognostic calculators (Adjuvant! and Numeracy) are widely used to individualize decisions regarding adjuvant therapy among patients with resected stage II and III colon cancer. However, these tools have not been directly compared. Hypothetical scenarios were formulated for the Numeracy calculator based on all potential combinations of age, lymph nodes status, tumor stage, and grade of tumor. These were then applied to three postsurgical therapy choices: observation, 5-fluorouracil (5-FU), or FOLFOX (5-FU, leucovorin, and oxaliplatin chemotherapy) to obtain the predicted 5-year disease-free survival (DFS) and overall survival (OS). Wilcoxon signed rank tests were used to compare the numerical predictions between the Adjuvant! and Numeracy calculators for each combination. A t...

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  Med Sci Monit 2010; 16(2):CR49-55 "Neoadjuvant treatment with weekly high-dose 5-Fluorouracil as a 24h-infusion, folinic acid and biweekly oxaliplatin in patients with primary resectable liver metastases of colorectal cancer: Long-term results of a phase II trial"

Conclusions: Neoadjuvant treatment with 5-FU combined with FA and L-OHP proved to be highly effective and well tolerated. Disease-free survival rates and median overall survival rates are promising. (Source: Medical Science Monitor)

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  A prospective monitoring of fatal serious adverse events (SAEs) in a Dutch Colorectal Cancer Group (DCCG) phase III trial (CAIRO) in patients with advanced colorectal cancer

Conclusions: There was little agreement between the relation as assessed by the local investigator compared with the IDMC. A quality control improves the assessment of safety results and the observed MPVs underscore the importance of educating medical staff and patients. (Source: Annals of Oncology)

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  Baseline physical functioning status of metastatic colorectal cancer patients predicts the overall survival but not the activity of a front-line oxaliplatin-fluoropyrimidine doublet.

CONCLUSIONS: Baseline self-reported PF independently predicted the OS of patients. Assessment of QoL should be incorporated in randomised trials evaluating the management of patients with MCRC. PMID: 20100144 [PubMed - in process] (Source: Acta Oncologica)

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  Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study

Conclusion  These data are insufficient to conclude with any certainty that the administration of Ca/Mg is not neuroprotective; however, the administration of Ca/Mg may not have any influence on antitumor activity and the blood concentration profile of platinum in patients receiving oxaliplatin-based chemotherapy. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10147-009-0015-3Authors Keiichiro Ishibashi, Saitama Medical University Department of Gastrointestinal and General Surgery, Saitama Medical Center 1981 Kamoda-Zujidocho Kawagoe Saitama 350-8550 JapanNorimichi Okada, Saitama Medical University Department of Gastrointestinal and General Surgery, Saitama Medical Center 1981 Kamoda-Zujidocho Kawagoe Saitama 350-8550 JapanTatsuya Miyazaki, Saitama M...

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  Two-stage laparoscopic liver resection for bilateral colorectal liver metastasis

Conclusion  Two-stage liver resections can be performed safely using laparoscopy. The intrahepatic Glissonian approach is a useful tool for pedicle control of the right liver, especially after previous dissection of the hilar plate. Content Type Journal ArticleCategory Dynamic ManuscriptDOI 10.1007/s00464-009-0859-7Authors M. A. Machado, University of São Paulo LIM-37; Department of Gastroenterology Rua Evangelista Rodrigues 407-05463-000 Sao Paulo BrazilF. F. Makdissi, University of São Paulo LIM-37; Department of Gastroenterology Rua Evangelista Rodrigues 407-05463-000 Sao Paulo BrazilR. C. Surjan, University of São Paulo LIM-37; Department of Gastroenterology Rua Evangelista Rodrigues 407-05463-000 Sao Paulo BrazilG. T. Kappaz, University of São Paulo LIM-37; Dep...

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  Oxaliplatin responses in colorectal cancer cells are modulated by CHK2 kinase inhibitors

Conclusions and implications: Combinations of CHK2 inhibitors with oxaliplatin should further sensitize cells to oxaliplatin treatment. However, these inhibitors produced an antagonistic effect on the response to oxaliplatin, which was reversed on the re-introduction of CHK2. These observations may have implications for the use of oxaliplatin in colorectal cancer therapy in combination with therapies targeting CHK2. (Source: British Journal of Pharmacology)

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  Management of isolated nonresectable liver metastases in colorectal cancer patients: a case-control study of isolated hepatic perfusion with melphalan versus systemic chemotherapy.

CONCLUSION: Compared with a patient group with comparable characteristics treated with systemic chemotherapy, IHP does not provide a benefit in overall survival in patients with isolated nonresectable colorectal liver metastases. Currently, the use of IHP cannot be advocated outside the scope of clinical studies. PMID: 20110289 [PubMed - as supplied by publisher] (Source: Ann Oncol)

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  Effects of lobaplatin and oxaliplatin on biological behavior of colorectal carcinoma cell line

Conclusion  Lobaplatin is a new antitumor platinum drug and can inhibit colorectal carcinoma cells. Moreover, lobaplatin could also inhibit colorectal carcinoma cells which are resistant to oxaliplatin. Content Type Journal ArticleDOI 10.1007/s10330-009-0185-5Authors Xue Bai, General Hospital of Beijing Command General Surgery Center of PLA Beijing 100700 ChinaBo Yu, General Hospital of Beijing Command General Surgery Center of PLA Beijing 100700 ChinaJunfeng Du, General Hospital of Beijing Command General Surgery Center of PLA Beijing 100700 ChinaShujun Yuan, General Hospital of Beijing Command General Surgery Center of PLA Beijing 100700 ChinaFuyi Zuo, General Hospital of Beijing Command General Surgery Center of PLA Beijing 100700 ChinaLiang Sun, General Hospital of ...

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  Oxaliplatin: Immune thrombocytopenia: case report

(Source: Reactions)

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  Phase II trial: Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer

Source: Lancet Oncology Area: News According to research published early online in the Lancet Oncology, intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk potentially operable rectal cancer, with acceptable safety and promising long-term outcomes.   In this phase II trial, researchers evaluated the safety and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in 105 rectal cancer patients. Patients received 12 weeks of neoadjuvant capecitabine and oxaliplatin (oxaliplatin 130 mg/m2 on day 1 with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks) followed by chemoradiotherapy (54 Gy over 6 weeks) with capecit...

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  Inhibition of Autophagy by Chloroquine Enhances Chemotherapy in an Orthotopic Murine Model of Pancreatic Cancer

Introduction: It is becoming increasingly clear that tumor cells utilize autophagy as a survival response when exposed to cytotoxic chemotherapy. We have previously demonstrated that targeted knockdown of the Receptor for Advanced Glycation End-products (RAGE) inhibits autophagy and increases susceptibility of cancer cells to chemotherapeutic toxicity. Chloroquine, a clinically available and relatively nontoxic drug currently used to treat rheumatologic disorders and malaria, is able to modulate autophagy by impeding fusion of the autophagosome with the lysosome, thus preventing an increase in autophagic flux. We hypothesized that inhibition of autophagy by chloroquine would increase the susceptibility of cancer cells to cytotoxic chemotherapy in an in vivo orthotopic model of mouse pancre...

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  Effects of Combination of EMAP II with Doxorubicin, Docetaxel, Oxaliplatin and Gemcitabine to Enhance Antitumor Activity in Pancreatic Cancer

Conclusions: In experimental PDAC, there is a differential effect to monotherapy with various cytotoxic agents. Addition of EMAP enhanced docetaxel and gemcitabine effects, but not those after doxorubicin or oxaliplatin. In vitro, EMAP addition increased the antiproliferative effects of doxorubicin, docetaxel and gemcitabine in HUVECs but not in ASPC PDAC cells. This antiendothelial combination therapy may represent an avenue to enhance clinical PDAC therapy with cell-cycle sensitive cytotoxic agents other than gemcitabine. (Source: Journal of Surgical Research)

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  Expression and Effects of IL-33 and Its Receptor in a Murine Pancreatic Cell Line

In this study, we analyzed the expression of IL-33 and ST2 and examined the effects of IL-33 on tumor cell proliferation and IL-33 inhibition by the soluble form of the ST2 receptor (sST2). Methods: Murine pancreatic PANCO2 and colorectal MC38 tumor cells were incubated for 24hours in the presence or absence of oxidative stress (H2O2, 100μM) or chemotherapeutic stress (oxaliplatin 100μM). IL-33 and ST2 expression was measured by real time PCR and by Western Blot. Cytoplasmic and nuclear lysates were obtained to assess the localization of IL-33. Cell proliferation was measured by CCK-8 assay after incubation for 24hours with various concentrations of IL-33 and sST2. Results: PANC02 and MC38 tumor cells showed moderate and low expression levels of ST2 receptor, respectively, compared to co...

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  Conference report (ASCO GI): Adjuvant XELOX regimen improves disease-free survival in elderly with colorectal cancer

Source: Reuters Health News, ASCO, MedPage Today Area: News According to the findings from a subanalysis of the XELOXA trial, XELOX (capecitabine + oxaliplatin) is associated with improved disease-free survival (DFS) over bolus 5-FU/LV regimens in stage III colon cancer, regardless of age. This research was presented at the ASCO 2010 Gastrointestinal Cancers Symposium (ASCO-GI; see the link below to access the abstract).   The authors note that a recent analysis of the ACCENT database, presented at ASCO 2009, concluded that newer adjuvant regimens are not associated with significant efficacy benefits versus 5-FU/LV in patients aged 70 years and above.  They therefore conducted a post-hoc analysis of the XELOXA trial (NO16968), which compared adjuvant treatment with XELOX ver...

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  Oxaliplatin Improves Outcomes in Elderly With Colorectal Cancer

In elderly colorectal cancer patients, a randomized phase 3 trial has shown better outcomes with adjuvant capecitabine and oxaliplatin than with standard 5-fluorouracil and leucovorin. Medscape Medical News (Source: Medscape Hematology-Oncology Headlines)

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  XELOX Improves Outcomes in Elderly With Colorectal Cancer

In elderly colorectal cancer patients, a randomized phase 3 trial has shown better outcomes with adjuvant capecitabine and oxaliplatin than with standard 5-fluorouracil and leucovorin. Medscape Medical News (Source: Medscape Today Headlines)

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  CapOx Improves Outcomes in Elderly With Colorectal Cancer

In elderly colorectal cancer patients, a randomized phase 3 trial has shown better outcomes with adjuvant capecitabine and oxaliplatin than with standard 5-fluorouracil and leucovorin. Medscape Medical News (Source: Medscape Hematology-Oncology Headlines)

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  MGMT −535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy

Conclusion  The MGMT −535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00432-010-0760-8Authors Jee Hyun Park, Kyungpook National University Hospital, Kyungpook National University School of Medicine Department of Internal Medicine Daegu KoreaNung Soo Kim, Kyungpook National University Hospital, Kyungpook National University School of Medicine Department of Internal Medicine Daegu KoreaJae Yong Park, Kyungpook National University Hospital, Kyungpook National University School of Medicine Department of Internal Medicine Daegu KoreaYee Soo Chae, Kyungpook National University Hospital, Kyungpook Nati...

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  ASCO GI: Regimen Benefits Colon Cancer Patients of All Ages

ORLANDO (MedPage Today) -- Patients with early-stage colorectal cancer benefit from adjuvant chemotherapy with capecitabine (Xeloda) and oxaliplatin (Oxalitin) regardless of age, according to a new analysis of data from a large, multicenter clinical trial. (Source: MedPage Today Gastroenterology)

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  Study teases out physician intent and preferences for CRC regimen selection

Fluorouracil, oxaliplatin (Eloxatin), and bevacizumab (Avastin) for first-line therapy is preferred in metastatic colon cancer. (Source: Cancer Network)

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  Urinary excretion of carnitine as a marker of proximal tubular damage associated with platin-based antineoplastic drugs

Conclusions. All platin derivatives investigated are associated with renal tubular damage in humans without significantly affecting glomerular function. The rapid onset and complete reversibility of this effect favour a functional mechanism such as impaired expression of OCTN2 in proximal tubular cells. (Source: Nephrology Dialysis Transplantation)

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  An association between transient hypokalemia and severe acute oxaliplatin-related toxicity predominantly in women.

Authors: Chay WY, Chew L, Yeoh TT, Tan MH PMID: 20092386 [PubMed - as supplied by publisher] (Source: Acta Oncologica)

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  Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy?

CONCLUSION: Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx. PMID: 20089559 [PubMed - as supplied by publisher] (Source: Ann Oncol)

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  Fixed-Dose Every-Other-Week Capecitabine and Oxaliplatin for Refractory Squamous Cell Carcinoma of the Head and Neck.

CONCLUSIONS:: Fixed-dose capecitabine and oxaliplatin combination on an every-other-week schedule showed activity in refractory SCCHN. The simplicity and toxicity profile of this regimen compares favorably with other commonly used chemotherapies and should be tested in larger studies. PMID: 20087165 [PubMed - as supplied by publisher] (Source: The American Journal of the Medical Sciences)

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  High-Grade Acute Organ Toxicity During Preoperative Radiochemotherapy as Positive Predictor for Complete Histopathologic Tumor Regression in Multimodal Treatment of Locally Advanced Rectal Cancer*

Conclusion:   Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors’ working group. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00066-009-2037-1Authors Hendrik Andreas Wolff, University Medicine Göttingen Department of Radiotherapy and Radiooncology Göttingen GermanyJochen Gaedcke, University Medicine Göttingen Department of Surgery Göttingen GermanyKlaus Jung, University Medicine Göttingen Department of Medical Statistics Göttingen GermanyRobert Michael Hermann, University Medicine Göttingen Department of Radiotherapy and Ra...

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  New Colon Cancer Quality Of Care Study Findings Have Been Reported

A report, 'Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer,' is newly published data in British Journal of Cancer. According to a study from France, "A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5- fluorouracil/leucovorin plus oxaliplatin (FOLFOX- 6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. (Source: Cancercompass News: Colorectal Cancer)

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  Matrix-assisted laser desorption/ionization imaging mass spectrometry of oxaliplatin derivatives in heated intraoperative chemotherapy (HIPEC)-like treated rat kidney.

Authors: Bouslimani A, Bec N, Glueckmann M, Hirtz C, Larroque C Oxaliplatin [1,2-diaminocyclohexane (dach)-Pt complex] is a platinum anticancer drug which is mainly used in the treatment of advanced colorectal cancer, particularly in Heated Intraoperative Chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis. In order to better understand the penetration of oxaliplatin in treated tissues we performed a direct imaging of tissue sections from HIPEC-like treated rat kidney using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. This procedure allowed the detection and localization of oxaliplatin and its metabolites, the monocysteine and monomethionine complexes, in kidney sections. Specifically, oxaliplatin and its metabolites were localized e...

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  Phase II study of combination chemotherapy with irinotecan and cetuximab for pretreated metastatic colorectal cancer harboring wild-type KRAS

Summary  The aim of this study was to prospectively evaluate the efficacy of combination irinotecan and cetuximab chemotherapy in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. KRAS status was evaluated using the Cycleave PCR method; only patients without KRAS mutations were included. Cetuximab was administered initially at 400 mg/m2 followed by weekly 250 mg/m2 infusions. Irinotecan was administered biweekly. From October 2008 to April 2009, a total of 30 patients were enrolled. The objective response rate was 30.0% (95% confidence interval [CI], 14.7–49.4%) and the disease control rate...

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  Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO) British Journal of Cancer advance online publication, January 12, 2010. doi:10.1038/sj.bjc.6605521 Authors: F Lordick, B Luber, S Lorenzen, S Hegewisch-Becker, G Folprecht, E Wöll, T Decker, E Endlicher, N Röthling, T Schuster, G Keller, F Fend & C Peschel (Source: British Journal of Cancer AOP)

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  The Evolving Role of Monoclonal Antibodies in Colorectal Cancer: Early Presumptions and Impact on Clinical Trial Development.

Authors: Eng C Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plat...

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  Differential transport of platinum compounds by the human organic cation transporter hOCT2 (hSLC22A2)

Conclusions and implications: The hSLC22A2 drug transporter is a critical determinant in the uptake and cytotoxicity of various platinum compounds, particularly oxaliplatin. (Source: British Journal of Pharmacology)

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  [Reflection and Reaction] Targeted therapy for biliary-tract cancer

Surgery is the only curative treatment option for biliary-tract cancer, but many patients are diagnosed at an unresectable stage. Furthermore, patients who undergo curative surgery often develop recurrences. Although chemotherapy is recognised as the standard treatment for patients with unresectable or recurrent biliary-tract cancer, a standard regimen was not previously defined because of a paucity of large randomised clinical trials. A recent, large phase 3 study showed a survival benefit with the combination of gemcitabine and cisplatin, compared with gemcitabine alone, in patients with unresectable biliary-tract cancer. The combination of gemcitabine and oxaliplatin also showed efficacy and safety in several phase 2 studies. Thus, the combination of gemcitabine and a platinum analogue,...

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  [Articles] Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([18F]FDG)-PET correlate with clinical outcome. (Source: The Lancet Oncology)

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  Xeloda in combination with oxaliplatin filed in Europe for the adjuvant treatment of patients with early colon cancer

Roche announced today that it has submitted an application to the European Medicines Agency (EMEA) to extend the label of Xeloda (capecitabine) for use in combination with oxaliplatin (XELOX) in the adjuvant (post-surgery) treatment of patients with early colon cancer. (Source: Roche Investor Update)

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  Xeloda in combination with oxaliplatin filed in Europe for the adjuvant treatment of patients with early colon cancer

Roche announced today that it has submitted an application to the European Medicines Agency (EMEA) to extend the label of Xeloda (capecitabine) for use in combination with oxaliplatin (XELOX) in the adjuvant (post-surgery) treatment of patients with early colon cancer. (Source: Roche Investor Update)

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  Oxaliplatin in first-line therapy for advanced non-small-cell lung cancer.

Authors: Raez LE, Kobina S, Santos ES Platinum doublets are the recommended standard first-line chemotherapy for stage IIIB/IV non-small-cell lung cancer (NSCLC). As efficacy outcomes associated with currently approved agents (cisplatin and carboplatin) are broadly similar, the decision about which platinum-based doublet to use is based on other factors such as toxicity. The goals for new platinum agents are to maintain and perhaps improve current efficacy and to improve toxicity. The aim of this article is to review the available clinical data from studies investigating the third-generation platinum analogue oxaliplatin in patients with advanced NSCLC. Information was obtained from the PubMed database and from recent presentations at national and international meetings. Oxaliplatin ha...

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  [Oxaliplatin and Leucovorin Plus Fluorouracil Versus Irinotecan and Leucovorin Plus Fluorouracil Combination Chemotherapy as a First-line Treatment in Patients with Metastatic or Recurred Gastric Adenocarcinoma.]

Conclusions: Both combination treatment can be used safely and effectively in recurred or metastatic gastric adenocarcinoma. PMID: 20098064 [PubMed - in process] (Source: Korean J Gastroenter...)

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  Fournier's gangrene as a possible side effect of bevacizumab therapy for resected colorectal cancer.

We present a case of a 67-year-old man who developed Fournier's gangrene during treatment with bevacizumab 4 months after completing mFOLFOX6 (5-FU/leucovorin/oxaliplatin) for CRC. Other than bevacizumab, the patient had no medications and had no medical conditions that would predispose to Fournier's gangrene. PMID: 20100690 [PubMed - in process] (Source: Clinical Colorectal Cancer)

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  Evolution of capecitabine dosing in colorectal cancer.

Authors: Sun W Fluoropyrimidines remain the cornerstone of chemotherapy regimens in the treatment of metastatic colorectal cancer (mCRC), even with the availability of newer cytotoxic and targeted biologic agents (eg, irinotecan, oxaliplatin, bevacizumab, cetuximab, and panitumumab). Though 5-fluorouracil (5-FU) can be administered via bolus or infusional schedules, the intermittent infusional schedule has been a mainstay of fluoropyrimidine-based regimens. This strategy, however, requires the insertion of central venous catheters and infusion pumps, which represent major inconveniences for patients and are associated with an increased risk for complications. Capecitabine is an orally administered fluoropyrimidine carbamate that is absorbed intact from the gastrointestinal tract and be...

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  Silencing Fas-associated phosphatase 1 expression enhances efficiency of chemotherapy for colon carcinoma with oxaliplatin.

CONCLUSION: RNA interference combined with conventional chemotherapy is more effective against colon cancer. PMID: 20039457 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

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  Clinical features of hypersensitivity reactions to oxaliplatin among Chinese patients with colorectal cancer.

Conclusion: Oxaliplatin-induced allergic reactions occurred in Chinese patients with CRC, and the incidence rate, occurrence time, degree of severity, and clinical outcome were consistent with literature published abroad. PMID: 20038320 [PubMed - in process] (Source: Ai Zheng)

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  St John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C gamma and varepsilon activity.

Authors: Galeotti N, Vivoli E, Bilia AR, Vincieri FF, Ghelardini C Current pharmacological treatments for neuropathic pain have limited efficacy and severe side-effect limitations. St. John's Wort (SJW) is a medicinal plant, mainly used as antidepressant, with a favourable side-effect profile. We here demonstrate the ability of SJW to relieve neuropathic pain in rat models. The antihyperalgesic profile and mechanism of action of SJW and its main components was studied in two rat models of neuropathic pain: the chronic constriction injury and the repeated administration of oxaliplatin. SJW, acutely administered at low doses (30-60mgkg(-1) p.o.), reversed mechanical hyperalgesia with a prolonged effect, being effective up to 180min after injection. Further examinations of the SJW main co...

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  Case report Combination of monoclonal antibody (Bevacizumab) and chemotherapy (FOLFIRI) in palliative treatment of metastatic adenocarcinoma of the small bowel (SBC): case report and review of the literature.

Small bowel cancer (SBC) is very rare malignancy. Annually about only 89 new cases of SBC are diagnosed in Poland (0.1-0.3%) of all malignancies and approximately 1% of gastrointestinal cancers. The prognosis of metastatic SBC is rather poor. The median survival of patients undergoing chemotherapy is approximately 14 months. Small bowel cancer is considered refractory to chemotherapy. Various anticancer agents have been tested in palliative chemotherapy of SBC: 5-Fluorouracil (5-FU), Cisplatin, Adriamycin, Mitomycin C, Oxaliplatin, Irinotecan, Carboplatin. Here we report a rare case of metastatic SBC with complete response (CR) after combination treatment with monoclonal antibody (Bevacizumab) and FOLFIRI (5-FU, Leukovorin, Irinotecan). The patient is alive without disease progression 28 m...

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  Amelioration of Oxaliplatin Neurotoxicity by Drugs in Humans and Experimental Animals: A MiniReview of Recent Literature

Abstract: The broad spectrum anti-neoplastic drug oxaliplatin is a third-generation platinum compound that inhibits DNA synthesis, mainly by causing intrastrandal cross-links in DNA. The drug is particularly useful alone and in combination with flurouracil and leucovorin in colorectal cancer, but it is also used for other cancers such as those of the ovary, lung, breast and liver, as well as non-Hodgkin's lymphoma. The drug is known to cause neurological, gastrointestinal and haematological toxicities. Neurotoxicity occurs in most of the treated patients and is considered to be a serious limitation for the use of the drug. The mechanism of the neurotoxicity is not known with certainty but may involve prolongation of sodium channels opening. Strategies to ameliorate oxaliplatin neurotoxicit...

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  Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion in Women with Heavily Pretreated Recurrent Ovarian Cancer

Conclusions  In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease. Content Type Journal ArticleCategory Gynecologic OncologyDOI 10.1245/s10434-009-0878-6Authors Wim P. Ceelen, University Hospital Department of Surgery Ghent BelgiumYves Van Nieuwenhove, University Hospital Department of Surgery Ghent BelgiumSimon Van Belle, University Hospital Department of Medical Oncology Ghent BelgiumHannelore Denys, University Hospital Department of Medical Oncology Ghent BelgiumPiet Pattyn, University Hospital Department of Surgery Ghent Belgium Journal ...

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  Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6

Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR). The present study investigated the association between germline genetic polymorphisms and the treatment outcome of cetuximab plus modified leucovovin, fluorouracil, and oxaliplatin (FOLFOX)6 chemotherapy in advanced gastric cancer (AGC). DNA from peripheral blood mononuclear cells of 38 patients enrolled in a phase II study of cetuximab plus modified FOLFOX6 were analyzed for 16 polymorphisms in eight genes (EGFR, epidermal growth factor, transforming growth factor-[alpha] (TGFA), thymidylate synthase, excision repair cross-complementation group 1, Xeroderma pigmentosum group D, and fragment c gamma receptors (FCGR)2A and 3A). The EGFR intron 1 CA repeat polymorphism was associated with survival. Twenty-o...

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  Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy

Conclusion  The MMR status or p53 positivity was not significantly associated with outcomes to FOLFOX as adjuvant chemotherapy in colon cancer patients with R0 resection. Adding oxaliplatin in adjuvant chemotherapy may overcome negative impact of 5-FU on colon cancers with MSI-H/MMR-D. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-009-1206-3Authors Seung Tae Kim, Sungkyunkwan University School of Medicine Divisions of Hematology-Oncology, Department of Medicine, Samsung Medical Center 50 Irwon-dong Gangnam-gu, Seoul 135-710 South KoreaJeeyun Lee, Sungkyunkwan University School of Medicine Divisions of Hematology-Oncology, Department of Medicine, Samsung Medical Center 50 Irwon-dong Gangnam-gu, Seoul 135-710 South KoreaSe Hoon Park, Sungkyunkwa...

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  Oxaliplatin for Chemotherapeutic Treatment and Prevention of Experimental Peritoneal Carcinomatosis in Rats Comparing the Intraperitoneal and Intravenous Application Mode

Eur Surg Res 2010;44:74-81 (DOI:10.1159/000269932) (Source: European Surgical Research)

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  Cellular and molecular mechanisms for the synergistic cytotoxicity elicited by oxaliplatin and pemetrexed in colon cancer cell lines

Conclusion  These data demonstrate that oxaliplatin and pemetrexed synergistically interact against colon cancer cells, through modulation of cell cycle, inhibition of Akt phosphorylation, induction of apoptosis and modulation of gene expression. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-009-1195-2Authors Sara Nannizzi, University of Pisa Division of Pharmacology and Chemotherapy, Department of Internal Medicine 56126 Pisa ItalyGareth J. Veal, Newcastle University Northern Institute for Cancer Research, Medical School Newcastle upon Tyne NE2 4HH UKElisa Giovannetti, University of Pisa Division of Pharmacology and Chemotherapy, Department of Internal Medicine 56126 Pisa ItalyValentina Mey, University of Pisa Division of Pharmacology and Chem...

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  A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX30 and chronomodulated XELOX30 as first-line therapy in patients with advanced colorectal cancer

Conclusion: XELOX30Chron does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy. (Source: Annals of Oncology)

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  Oxaliplatin-Induced Lhermitte's Phenomenon as a Manifestation of Severe Generalized Neurotoxicity

Oncology 2009;77:342-348 (DOI:10.1159/000265940) (Source: Karger Publishers)

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  Surgery for rare aneurysm associated with colorectal cancer.

We report a case of rectal cancer and concomitant aneurysm from the ascending aorta to the common iliac artery. As with DeBakey type I aortic dissecting aneurysm, our patient was treated by rectal cancer resection, with preservation of the anus (Dixon operation) under controlled hypotension. Blood pressure was maintained at 80-90/50-60 mmHg and the pulse at 70-90 beats/min. The pathological examination of the surgical specimen showed a poorly differentiated T3N0 tumor. The patient had an uneventful recovery without aneurysm rupture, and was discharged from hospital on postoperative day 15 after 3 d adjuvant chemotherapy with oxaliplatin combined with calcium folinate and fluorouracil. The patient was given six courses of adjuvant chemotherapy in 6 mo, without recurrence or metastasis, and ...

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  Increased levels and defective glycosylation of MRPs in ovarian carcinoma cells resistant to oxaliplatin.

Authors: Beretta GL, Benedetti V, Cossa G, Assaraf YG, Bram E, Gatti L, Corna E, Carenini N, Colangelo D, Howell SB, Zunino F, Perego P Pt compounds still represent the mainstay of the treatment of ovarian carcinoma. The aim of the present study was to investigate the molecular bases of resistance to Pt drugs using an oxaliplatin-resistant ovarian carcinoma cell model IGROV-1/OHP. These cells exhibited high levels of resistance to oxaliplatin, cross-resistance to cisplatin and topotecan and displayed a marked accumulation defect of Pt drugs. This feature was associated with increased expression and altered N-linked glycosylation of ATP binding cassette transporters MRP1 and MRP4. Pre-treatment with tunicamycin, which inhibits the biosynthesis of N-linked oligosaccharides, decreased the...

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  The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay

Conclusions: Combining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a substantial recovery between radiation fractions. This mucosal-sparing effect achieved by fractionation was maintained also when chemotherapy was added. (Source: Radiation Oncology)

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  Emodin enhances sensitivity of gallbladder cancer cells to platinum drugs via glutathion depletion and MRP1 downregulation.

In conclusions, emodin can work as an adjunct to enhance the anti-cancer effect of platinum drugs in gallbladder cancer cells via ROS-related mechanisms. PMID: 20005210 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology)

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  KRAS and BRAF Mutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial [Gastrointestinal Cancer]

Conclusion KRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents. (Source: Journal of Clinical Oncology)

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  A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer

Conclusions Cetuximab in combination with XELOX chemotherapy was active and safe as first-line treatment of metastatic and/or recurrent AGC patients. Content Type Journal ArticleCategory PHASE II STUDIESDOI 10.1007/s10637-009-9363-0Authors Chul Kim, Asan Medical Center, University of Ulsan College of Medicine Department of Oncology 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 South KoreaJae-Lyun Lee, Asan Medical Center, University of Ulsan College of Medicine Department of Oncology 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 South KoreaMin-Hee Ryu, Asan Medical Center, University of Ulsan College of Medicine Department of Oncology 86 Asanbyeongwon-gil, Songpa-gu Seoul 138-736 South KoreaHeung Moon Chang, Asan Medical Center, University of Ulsan College of Medicine Department of O...

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  Genome-wide identification of chemosensitive single nucleotide polymorphism markers in colorectal cancers

Improved methods for predicting chemoresponsiveness involving the identification of polymorphic markers is highly desirable, considering narrow therapeutic index and frequent resistance to anti-cancer regimens. The genome-wide screening of chemosensitive single nucleotide polymorphisms (SNPs) was undertaken in association with in vitro chemosensitivity assays in 104 colorectal cancer patients for the initial screening step. Allele frequency, linkage disequilibrium, potential function, and Hardy[ndash]Weinberg equilibrium of the candidate SNPs were then determined for the identifying step. Finally, clinical association analysis in the other 260 evaluable patients or cell viability assays of transfected RKO cells was used to verify candidate SNPs for the validation step. In total, 12 SNPs to...

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  Goshajinkigan (GJG) Herbal Supplement for Neuropathy

In this study, GJG reduced the rate of neuropathy by half. Is GJG for You? Goshajinkigan (GJG) is a Japanese herbal preparation that can contain up to 10 different herbs. For this reason, it may be difficult to obtain exactly the same herbal formula that was used in this study. If you are going to be receiving chemotherapy that can cause neuropathy, talk to your doctor about all of the options available for managing and preventing this side effect. There are medications that may help and other dietary supplements that are more easily obtained in the US, such as glutamine (a protein supplement). It's unlikely that your doctor will have heard of Goshajinkigan, because it is not regularly used or available in the US. You can print out a copy of this research and share it with your doctor. He ...

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  Vascular Endothelial Growth Factor Plus Epidermal Growth Factor Receptor Dual Targeted Therapy in Metastatic Colorectal Cancer: Synergy or Antagonism?

There has been an intensive effort to develop novel therapies for the treatment of metastatic colorectal cancer (mCRC). The anti-epidermal growth factor receptor (EGFR) antibodies panitumumab and cetuximab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab have demonstrated clinical efficacy and acceptable toxicity in the treatment of mCRC as single agents or in combination with chemotherapy. Recent clinical trials have explored the efficacy and safety of treatment regimens incorporating chemotherapy in combination with bevacizumab and either panitumumab or cetuximab in patients with mCRC. Results from the BOND-2 trial, which investigated cetuximab, bevacizumab, and chemotherapy in mCRC, provided support for this therapeutic approach. Two large randomized phase 3 t...

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  Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel.

In conclusion, the combinations with oxaliplatin showed a synergistic effect in the combination studies. Although the combinations with docetaxel did not show an enhanced effect in the in vitro studies, this combination revealed an increased effect in the xenograft model. PMID: 19956857 [PubMed - in process] (Source: International Journal of Oncology)

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  [Rectal cancer and adjuvant chemotherapy: which conclusions?]

Authors: Bachet JB, Rougier P, Gramont AD, André T Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the "historical studies" of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study s...

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  Biomarkers and anti-EGFR therapies for KRAS wild-type metastatic colorectal cancer

Abstract  Therapy for metastatic colorectal cancer has been improved in terms of response rate, time to progression and overall survival by the emergence of anti-EGFR monoclonal antibodies (cetuximab and panitumumab) in combination with standard cytotoxic chemotherapy (oxaliplatin or CPT-11-based combinations). However, the benefits of cetuximab and panitumumab are confined to KRAS wild-type (KRAS-wt) colorectal tumours; KRAS-mutated tumours rarely respond to these drugs. Of all colorectal tumours, 65% are KRAS-wt tumours, but anti-EGFR therapies are effective for only 60–70% of these. Therefore, other biomarkers and molecular pathways must be involved in the response to anti-EGFR therapies in KRASwt colorectal tumours. Factors that may explain the lack of response includ...

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  The combination of ERCC1 and XRCC1 gene polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer

Conclusions  This is the first study which showed that polymorphisms of ERCC1 and XRCC1, in combination not individually, were independent predictors for DCR and OS. This may contribute to the selection of patients who would benefit from oxaliplatin-based chemotherapy for metastatic colorectal cancer. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-009-1186-3Authors Jun Liang, Qing Dao University Department of Oncology, The Affiliated Hospital of Medical College 266003 Qingdao ChinaTao Jiang, Qing Dao University Department of Oncology, The Affiliated Hospital of Medical College 266003 Qingdao ChinaRu-yong Yao, Qing Dao University Central Laboratory, The Affiliated Hospital of Medical College 266003 Qingdao ChinaZi-min Liu, Qing Dao University De...

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  The effect of DNA mismatch repair (MMR) status on oxaliplatin-based first-line chemotherapy as in recurrent or metastatic colon cancer

This study investigated the effect of MMR status on the treatment outcomes for CAPOX and FOLFOX as first-line combination chemotherapy in recurrent or metastatic colon cancer. We analyzed 171 patients who had been treated with CAPOX or FOLFOX as first-line combination chemotherapy in recurrent or metastatic colon adenocarcinoma between February 2004 and July 2008. Tumor expression of the MMR proteins, MLH1 and MSH2, was detected by immunohistochemistry (IHC) in surgically resected tumor specimens. The microsatellite instability (MSI) was analyzed by polymerase chain reaction (PCR) amplification, using fluorescent dye-labeled primers specific to microsatellite loci. Tumors with MMR defect were defined as those demonstrating a loss of MMR protein expression (MMR-D) and/or a microsatell...

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  Elimination of Colon Cancer Stem-Like Cells by the Combination of Curcumin and FOLFOX.

In conclusion, our data suggest that curcumin by itself or together with the conventional chemotherapeutic could be an effective treatment strategy for preventing the emergence of chemoresistant colon cancer cells by reducing/eliminating CSCs. PMID: 19956394 [PubMed - in process] (Source: Translational Oncology)

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  [Chemotherapy for colorectal cancer.]

Authors: Hong YS, Kim TW Recent advances in chemotherapy lead to improved survival outcomes in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the important chemotherapeutic agents since 1950s, but the introduction of newer cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have changed treatment strategies for these patients. A deliberate choice should be made for adjuvant chemotherapy, because it has became complicated more than ever before. Oxaliplatin plus 5-FU seemed to be superior in terms of disease-free and overall survival than 5-FU alone after curative surgery for colon cancers. However not all of these patients seemed to receive benefit from this intensive adjuvant treatment, and some limitations are presen...

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  Fluorouracil/folinic acid/oxaliplatin: Diffuse alveolar damage: case report

(Source: Reactions)

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  Oxaliplatin: Immediate- and late-onset allergic reactions: 25 cases

(Source: Reactions)

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  Water-soluble Organometallic Analogues of Oxaliplatin with Cytotoxic and Anticlonogenic Activity.

Authors: Benedetti M, Antonucci D, Migoni D, Vecchio VM, Ducani C, Fanizzi FP PMID: 19950163 [PubMed - as supplied by publisher] (Source: ChemMedChem)

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  Colon cancer and the elderly: From screening to treatment in management of GI disease in the elderly

Colorectal cancer is one of the commonest tumours in the Westernized world affecting mainly the elderly. This neoplasm in older individuals occurs more often in the right colon and grows more rapidly than in the young, often shows a mucinous histology and mismatch repair gene changes. Effective screening permits discovery of colorectal cancer at an early highly treatable stage and allows for detection and removal of premalignant colorectal adenomas. Screening methods that focus on cancer detection use fecal assays for the presence of blood or altered DNA, those for detection of adenomas (and early cancer) use endoscopic or computerised radiologic techniques. Broad use of screening methods has lowered colorectal cancer development by about 50%. In addition, prevention of the earliest stage ...

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  An open label randomized multicentre phase IIIb trial comparing parenteral substitution versus best supportive nutritional care in subjects with pancreatic adenocarcinoma receiving 5-FU plus oxaliplatin as 2nd or higher line chemotherapy regarding clinical benefit - PANUSCO

DiscussionThe aim of this clinical trial is to evaluate whether parenteral nutrition in combination with defined 2nd line or higher chemotherapy has an impact on quality of life for patients suffering from pancreatic adenocarcinoma.Trial registrationCurrent Controlled Trials ISRCTN60516908. (Source: BMC Cancer)

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  Bevacizumab Added to Gemcitabine and Oxaliplatin for Biliary-Tract Cancer

Adding bevacizumab to chemotherapy for advanced biliary-tract cancer improved outcomes, according to a new study. The phase II trial, conducted at Massachusetts General Hospital Cancer Center in Boston,... (Source: OncologySTAT What Patients Are Reading)

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  Ursodeoxycholic acid switches oxaliplatin-induced necrosis to apoptosis by inhibiting reactive oxygen species production and activating p53-caspase 8 pathway in HepG2 hepatocellular carcinoma

In conclusion, UDCA switches oxaliplatin-induced necrosis to apoptosis via inhibition of ROS production and activation of the p53-caspase 8 pathway in HepG2 cells. As necrosis and subsequent inflammation are implicated in tumor progression and malignancy, our results imply a potential improved efficacy of UDCA-combined chemotherapy in HCC by reducing inflammatory responses that may be triggered by oxaliplatin. (Source: International Journal of Cancer)

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  OPTIMOX2 study examines if 5-FU maintenance therapy is necessary in unresectable metastatic colorectal cancer?

Source: J Clin Oncol Area: News The GERCOR OPTIMOX1 study showed that stopping oxaliplatin after six cycles of infusional FU, LV, and oxaliplatin chemotherapy (FOLFOX7) in patients with advanced colorectal cancer then continuing maintenance therapy with a simplified LV plus bolus and infusional FU regimen alone achieves equivalent efficacy results to continuing FOLFOX4 until progression or toxicity. Stopping oxaliplatin after six cycles also reduced toxicity. The GERCOR OPTIMOX2 study evaluated whether FU maintenance therapy is really necessary, i.e. could a complete treatment break (chemotherapy-free interval) be given before reintroducing FOLFOX treatment? It was to have randomised 600 patients to allow detection of a 20% absolute difference in 2-year survival. However, the investigator...

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  Can Chemotherapy Be Discontinued in Unresectable Metastatic Colorectal Cancer? The GERCOR OPTIMOX2 Study [Gastrointestinal Cancer]

Conclusion The planned complete discontinuation of chemotherapy had a negative impact on DDC and PFS compared with the maintenance therapy strategy. These results suggest that chemotherapy discontinuation cannot be decided before therapy is initiated in patients with advanced colorectal cancer. (Source: Journal of Clinical Oncology)

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  Oxaliplatin-induced proximal renal tubular acidosis

Content Type Journal ArticleCategory CE - Letter to the EditorDOI 10.1007/s11739-009-0331-7Authors Aurelio Negro, Santa Maria Nuova Hospital Second Unit of Internal Medicine, Department of Internal Medicine viale Risorgimento, 80 42100 Reggio Emilia ItalyChiara Grasselli, Santa Maria Nuova Hospital Second Unit of Internal Medicine, Department of Internal Medicine viale Risorgimento, 80 42100 Reggio Emilia ItalyPaola Galli, Santa Maria Nuova Hospital Second Unit of Internal Medicine, Department of Internal Medicine viale Risorgimento, 80 42100 Reggio Emilia Italy Journal Internal and Emergency MedicineOnline ISSN 1970-9366Print ISSN 1828-0447 (Source: Internal and Emergency Medicine)

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  Cetuximab “boosts cancer outcomes”

Neoadjuvant treatment with irinotecan or oxaliplatin-based chemotherapy can shrink tumours to allow for surgery, says new report (Source: Pharmacy Europe)

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  Horizon scanning: Phase II study finds that cetuximab may increase resectability of colorectal liver metastases

Source: Lancet Oncology Area: News According to the results of a Phase II study published early online in Lancet Oncology, the addition of cetuximab to standard neoadjuvant chemotherapy for unresectable colorectal liver metastases increased the proportion of lesions that were rendered eligible for curative resection.   A total of 114 patients with non-resectable liver metastases (technically non-resectable or ?5 metastases) were randomised (non-blinded) to receive cetuximab in addition to FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A, n=56) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B, n=55). Tumour response (primary endpoint) was evaluated every 8 weeks (CT or MRI) and resectability was reassessed after 16 weeks and then every 2 months up to 2 ...

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  Roche champions Avastin for NHS use

Bevacizumab-based drug rejected by NICE has been shown to shrink tumours in 78% of patients when added to capecitabine and oxaliplatin (Source: Pharmacy Europe)

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  NICE issues ACD on bevacizumab with oxaliplatin and either 5-fluorouracil or capecitabine for the treatment of metastatic colorectal cancer

Source: NICE Area: News The National Institute for Health and Clinical Excellence has issued an appraisal consultation document on the use of bevacizumab in combination with oxaliplatin and either 5-fluorouracil or capecitabine for the treatment of metastatic colorectal cancer. The preliminary recommendations are as follows: . Bevacizumab in combination with oxaliplatin and either 5?fluorouracil plus folinic acid or capecitabine is not recommended for the treatment of metastatic colorectal cancer. . People currently receiving bevacizumab in combination with oxaliplatin for the treatment of metastatic colorectal cancer should have the option to continue treatment until they and their clinicians consider it appropriate to stop.   The closing date for comments is 14 Dece...

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  Phase I Study of Flavopiridol with Oxaliplatin and Fluorouracil/Leucovorin in Advanced Solid Tumors.

CONCLUSIONS: Flavopiridol with FOLFOX is a safe and tolerable regimen. Promising clinical activity was seen across tumor types. Encouraging results in the platinum-refractory germ cell tumor population has prompted a phase II trial that is currently open for accrual. (Clin Cancer Res 2009;15(23):7405-11). PMID: 19934304 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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  Bevacizumab plus gemcitabine/oxaliplatin showed antitumor activity in advanced biliary-tract cancers

(Source: HemOncToday.com)

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  Advanced Biliary-Tract Cancers: Promising New Drug Regimen

An article published Online First in The Lancet Oncology reports that bevacizumab given in addition to the combined chemotherapy regimen of gemcitabine and oxaliplatin (GEMOX-B) is well tolerated. In addition, it shows promising antitumor activity in patients with advanced biliary-tract cancers. (Source: Health News from Medical News Today)

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  Advanced Biliary-Tract Cancers: Promising New Drug Regimen

An article published Online First in The Lancet Oncology reports that bevacizumab given in addition to the combined chemotherapy regimen of gemcitabine and oxaliplatin (GEMOX-B) is well tolerated. In addition, it shows promising antitumor activity in patients with advanced biliary-tract cancers. The article reviews the survival and tumour response that compare favourably with earlier studies in patients treated with GEMOX alone. Further investigation in randomised trials is needed. (Source: Cancer / Oncology News From Medical News Today)

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  Drugs Deemed Safe, Effective for Biliary Tract Cancers

Combination treatment with bevacizumab, gemcitabine, and oxaliplatin is safe and effective in treating advanced biliary-tract cancers, with positron emission tomography scanning predicting treatment response and outcomes, according to a study published online Nov. 23 in The Lancet Oncology. (Source: Modern Medicine)

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  Phase I study of 3-weekly docetaxel, capecitabine and oxaliplatin combination chemotherapy in patients with previously untreated advanced gastric cancer

Conclusion  The RD of the DXO regimen in patients with AGC is capecitabine 1,000 mg/m2 twice daily on days 1–14, in combination with decetaxel 60 mg/m2 (day 1) and oxaliplatin 100 mg/m2 (day 1) repeated every 3 weeks. The DXO regimen seems to have promising activity and offers an easy alternative to DCF. The toxicities appear to be still substantial, but manageable. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s00280-009-1171-xAuthors Sun Jin Sym, University of Ulsan College of Medicine Division of Oncology, Department of Medicine, Asan Medical Center 388-1 Pungnap-2 Dong, Songpa Gu Seoul 138-736 KoreaMin-Hee Ryu, University of Ulsan College of Medicine Division of Oncology, Department of Medicine, Asan Medical Center 388-1 Pung...

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  Research Conducted At University Of Texas Has Updated Our Knowledge About Colon Cancer

According to recent research from the United States, Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer (CRC) in both the adjuvant treatment and metastatic disease settings. Significant improvements in outcomes have been achieved with oxaliplatin-based combinations in these settings when compared with administration of 5-fluorouracil alone. (Source: Cancercompass News: Colorectal Cancer)

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  [Therapeutic effect of docetaxel combined with oxaliplatin for treatment of recurrent epithelial ovarian cancer.]

CONCLUSION: Combination of DTX and OXA produces good therapeutic effect with tolerable toxicity profile for treatment of recurrent epithelial ovarian cancer. PMID: 19923093 [PubMed - as supplied by publisher] (Source: Journal of Southern Medical University)

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  Comparison of the Clinical Effects of Paclitaxel and Paclitaxel plus Oxaliplatin as the Second-line Treatment of Advanced Non-small Cell Lung Cancer

Conclusion Singlepaclitaxel administration as the second-lined treatment of advanced NSCLC is tolerable and has the response effect no worse than the combined chemotherapy. (Source: Chinese Journal of Lung Cancer)

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  Influence of GSTP1 I105V polymorphism on cumulative neuropathy and outcome of FOLFOX-4 treatment in Asian patients with colorectal carcinoma

Glutathione S-transferase P1 (GSTP1) participates in detoxification of potentially genotoxic compounds that may alter the efficacy and toxicity of platinum-based chemotherapy. We analyzed the influence of I105V polymorphism of GSTP1 on clinico-pathological features and outcomes in 166 Chinese patients with metastatic colorectal carcinoma who had been treated with first-line FOLFOX-4. Combined analysis of GSTP1 I105V, ERCC1-118, and XPD-751 polymorphisms was also conducted. The results showed that, in comparison with Caucasian populations, a remarkably lower prevalence of Val105 allele variants was noted (24.7%). Patients with Val105 allele variants had a higher response to FOLFOX-4 (56.1%vs 37.6%, P = 0.04), and a longer progression-free (P < 0.01) as well as overall (P < 0.01) survival. B...

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  An Msh2 Conditional Knockout Mouse for Studying Intestinal Cancer and Testing Anticancer Agents

Conclusions: Msh2LoxP/LoxP mice in combination with appropriate Cre recombinase transgenes have excellent potential for preclinical modeling of Lynch syndrome, MMR-deficient tumors of other tissue types, and use in drug development. (Source: Gastroenterology)

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  Association of Molecular Markers With Toxicity Outcomes in a Randomized Trial of Chemotherapy for Advanced Colorectal Cancer: The FOCUS Trial [Gastrointestinal Cancer]

Conclusion These results do not support the routine clinical use of the evaluated polymorphisms, including UGT1A1*28. Further investigation of XRCC1, ERCC2, and GSTP1 as potential predictors of irinotecan toxicity is warranted. (Source: Journal of Clinical Oncology)

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  Oxaliplatin-induced gamma-H2AX activation via both p53-dependent and -independent pathways but is not associated with cell cycle arrest in human colorectal cancer cells.

In this study, we investigated the roles of p53 and gamma-H2AX following oxaliplatin treatment, as they are important effector proteins for apoptosis and DSB repair, respectively. Both phosphorylated-p53 (Ser-15) and gamma-H2AX were up-regulated and accumulated in the nuclei of p53-wild type human colorectal cancer HCT116 cells after exposure to oxaliplatin. Concomitantly, oxaliplatin-induced G2/M arrest was associated with a reduction in both cyclin B1 expression and phosphorylated-CDC2 (Thr-161). Release of G2/M arrest by caffeine was accompanied by a decrease in the levels of p53/p21; however, gamma-H2AX levels were unchanged. Furthermore, inhibition of p53 phosphorylation by pifithrin-alpha was sufficient to reduce the oxaliplatin-induced up-regulation of gamma-H2AX and apoptosis. Oxal...

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  Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue

Background: Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel. Results: After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; P (Source: Molecular Pain)

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  Cost-effectiveness of oxaliplatin in the adjuvant treatment of colon cancer in Canada

Conclusions With an incremental cost of CA$24,104 per qaly gained, folfox is a cost-effective adjuvant treatment for stage iii colon cancer. Compared with 5fu/lv alone, this regimen offers better clinical outcomes and provides good value for money. (Source: Current Oncology)

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  Oxaliplatin: Haemolytic anaemia: case report

(Source: Reactions)

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  Implications of KRAS mutation status for the treatment of metastatic colorectal cancer

Abstract  Targeted agents have become an integral part of the treatment of a number of malignant diseases and regimens containing agents that disrupt the epidermal growth factor receptor (EGFR) signaling pathway are now considered a standard therapeutic approach for a range of tumor types. Recently, the mutational status of the KRAS gene in tumors was shown to be predictive of outcome to treatment with EGFR-targeted therapies in metastatic colorectal cancer (mCRC). The immoglobulin (Ig) G1 EGFR-targeting monoclonal antibody (mAb), cetuximab, has been shown to provide significant clinical benefits when added to standard irinotecan- and oxaliplatin-containing chemotherapy regimens, first-line, in patients with KRAS wild-type mCRC. Its effects on tumor response and resectabilit...

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  Oxaliplatin: Acute haemolysis in an elderly patient: case report

(Source: Reactions)

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  Oxaliplatin: Delayed RPLS: case report

(Source: Reactions)

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  Overview of Systemic Therapy for Colorectal Cancer

Clinics in Colon and Rectal Surgery 2009; 22: 251-256DOI: 10.1055/s-0029-1242465ABSTRACTColorectal cancer (CRC) is the third most common cancer and second leading cause of death from cancer in North America. The authors provide an overview of the indications for both chemotherapy and targeted therapy, as well as discuss the efficacy and toxicity of systemic therapy. They highlight the key studies that lead to the initial historical use of fluorouracil (5FU) based chemotherapy in the adjuvant and metastatic setting, the recent adoption of 5FU plus leucovorin (LV) and oxaliplatin (FOLFOX) chemotherapy over 5FU when treating adjuvant patients, and the use of FOLFOX or 5FU plus LV and irinotecan (FOLFIRI) in metastatic patients. They also review the role of chemotherapy in treating rectal canc...

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  Amgen Announces Overall Survival Results For Vectibix(R) In First-Line Metastatic Colorectal Cancer

Amgen (Nasdaq: AMGN) announced that the Phase 3 PRIME "203" trial evaluating Vectibix® (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC) failed to meet a secondary endpoint of overall survival. (Source: Health News from Medical News Today)

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  Amgen Announces Overall Survival Results For Vectibix(R) In First-Line Metastatic Colorectal Cancer

Amgen (Nasdaq: AMGN) announced that the Phase 3 PRIME "203" trial evaluating Vectibix® (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC) failed to meet a secondary endpoint of overall survival. (Source: Pharma Industry News From Medical News Today)

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  Amgen Announces Overall Survival Results for Vectibix(R) in First-Line Metastatic Colorectal Cancer

Amgen (Nasdaq: AMGN) today announced that the Phase 3 PRIME "203" trial evaluating Vectibix® (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC) failed to meet a secondary endpoint of overall survival. (Source: World Pharma News)

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  Amgen Announces Overall Survival Results for Vectibix(R) in First-Line Metastatic Colorectal Cancer

THOUSAND OAKS, Calif., Nov. 5 /PRNewswire-FirstCall/—Amgen (Nasdaq: AMGN) today announced that the Phase 3 PRIME "203" trial evaluating Vectibix (R) (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC) failed to meet a secondary endpoint of overall survival.  Earlier this year, it was announced that the trial met its primary endpoint by significantly prolonging progression-free survival (PFS) in the first-line treatment of patients with KRAS wild-type mCRC. (Source: Amgen News Service)

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  Docetaxel: its role in current and future treatments for advanced gastric cancer

Abstract  A globally accepted standard chemotherapy remains undetermined in gastric cancer, but the recent introduction of active “new-generation agents” such as taxanes, irinotecan (CPT-11), oxaliplatin, S-1, and capecitabine, offers hope for markedly improving patient outcomes. Docetaxel, as well as the other new-generation agents, plays a key role in the development of the new-era chemotherapy, and the incorporation of taxanes has provided several regimens, such as docetaxel/cisplatin/5-fluorouracil (5-FU) (DCF), that could become standard treatment. The DCF regimen is now regarded as a standard treatment option in advanced gastric cancer in selected patients in good condition. Many institutions and cooperative groups continue to study a variety of docetaxel-based co...

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  An animal model for chemotherapy-associated steatohepatitis and its prevention by the oral administration of fatty acid bile acid conjugate

Preoperative chemotherapy for hepatic resection of colorectal liver metastases is associated with the development of chemotherapy-associated steatohepatitis (CASH). This increases the risk of perioperative morbidity and mortality. To the authors' knowledge, an animal model for CASH has not been described previously. It has been established that fatty acid bile acid conjugates (FABACs) prevent the formation of diet-induced fatty liver. The current study was designed to establish an animal model of CASH and to use that model to study the effect of FABACs on its occurrence.C57BL/6 mice were given different doses of oxaliplatin and irinotecan. Oxaliplatin administered once weekly at a dose of 6 mg/kg for a total dose of 24 mg/kg was tolerated best and was associated most consistently with CASH...

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  Economic impact of alternative adjuvant chemotherapy regimens for stage III colon cancer.

CONCLUSIONS: In Germany, FOLFOX-4 is the most effective but also the most expensive treatment and represents the current standard. Xelox emerges as a slightly less costly alternative when oral treatment is preferred. For patients not able to tolerate oxaliplatin-based therapy, capecitabine has the best economic profile of all alternative regimens. Drug acquisition costs are by far the most important factor driving costs in all regimens. PMID: 19887868 [PubMed - in process] (Source: Onkologie)

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  Capecitabine/gemcitabine/oxaliplatin: Polymicrobial liver abscess in an elderly patient?: case report

(Source: Reactions)

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  Fluorouracil/oxaliplatin: Reversible posterior leukoencephalopathy syndrome: case report

(Source: Reactions)

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  Hepatic Toxicities Associated with the Use of Preoperative Systemic Therapy in Patients with Metastatic Colorectal Adenocarcinoma to the Liver.

Authors: Cleary JM, Tanabe KT, Lauwers GY, Zhu AX Colorectal cancer patients with isolated liver metastasis are potentially cured with surgical resection. Recent advances in systemic chemotherapy have increased the ability to convert unresectable metastatic liver lesions to resectable lesions. The cost in toxicity of these therapeutic advances is increasingly being recognized. Numerous reports have demonstrated an association between irinotecan and steatohepatitis as well as between oxaliplatin and sinusoidal dilation. In this review, we summarize the current clinical experience with these hepatic toxicities and discuss the role they play in determining postoperative morbidity. We also review emerging safety data regarding the use of bevacizumab and cetuximab. Finally, we give specific...

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  Chemotherapy: Adding oxaliplatin to the equation

Nature Reviews Clinical Oncology 6, 620 (2009). doi:10.1038/nrclinonc.2009.162 Author: Al B. Benson Pooled analyses from the Adjuvant Treatment of Colon Cancer trial suggest that most patients with stage III colon cancer develop recurrence within the first 3 years following treatment. Improved disease-free survival and improved overall survival were observed for such patients who were treated with adjuvant combination therapy of 5-fluorouracil, leucovorin and oxaliplatin versus those treated with 5-fluorouracil and leucovorin. (Source: Nature Clinical Practice Oncology)

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  Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study

Conclusions: The BEAT study shows that the efficacy and safety profile of bevacizumab in routine clinical practice is consistent with results observed in prospective randomised clinical trials and another large observational study in the United States (BRiTE study). (Source: Annals of Oncology)

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  Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma--correlation with excision repair cross-complementing-1 polymorphisms

Conclusions: GEMOX is active in the treatment of recurrent NPC. Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted. (Source: Annals of Oncology)

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  Hypoxic Single-Pass Isolated Hepatic Perfusion of Hypotonic Cisplatin: Safety Study in the Pig

Conclusions  A hypoxic single-pass isolated liver perfusion with hypotonic cisplatin is feasible and safe. Effluent from the liver is highly cytotoxic on cancer cells. A clinical study with 50 mg/L of hypotonic cisplatin is warranted in patients with unresectable liver metastases from colon cancer. Content Type Journal ArticleCategory Translational Research and BiomarkersDOI 10.1245/s10434-009-0775-zAuthors Pablo Ortega-Deballon, University of Burgundy INSERM UMR 866, School of Medicine Burgundy FranceOlivier Facy, University Hospital Department of Digestive and Thoracic Surgical Oncology Dijon FranceDavid Consolo, University Hospital Department of Anesthesiology Dijon FranceGuy Magnin, University Hospital Department of Anesthesiology Dijon FranceHervé Tixier, Un...

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