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- W830986802 abstract "Introduction The current standard of chemotherapy for newly diagnosed patients with advanced pancreatic cancer is either FOLFIRINOX (5-fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin) or gemcitabine/nab-paclitaxel regimens, but the 5-year survival rate is less than 5%. Conventional gemcitabine therapy requires weekly visits for patients, while the FOLFIRINOX regimen requires biweekly intravenous infusion therapy, and the gemcitabine/nab-paclitaxel regimen often causes progressive neuropathy, limiting the duration of therapy. An alternative therapy has been developed that greatly improves the tolerability of chemotherapy, reduces the time burden on patients, and provides better tolerance of the treatment-induced side effects, and yet maintains duration of overall survival (OS). This therapy is fixed-dose-rate infusion of gemcitabine with capecitabine. This therapy was particularly well-tolerated relative to the rather toxic FOLFIRINOX therapy, and relative to the neuropathy common with gemcitabine/nab-paclitaxel regimens, especially in patients with impaired marrow tolerance due to prior radiotherapy, or with pre-existing neuropathy. A therapy of weekly gemcitabine and capecitabine was described by Knox et al1 in the Journal of Clinical Oncology in 2005 for advanced biliary carcinomas, utilizing weekly gemcitabine on days 1 and 8, with capecitabine given at a dosage of 650 mg/m twice daily for 14 days; cycles were repeated every 21 days. Prolonged fixed-dose-rate infusions were developed with the knowledge that phosphorylation of gemcitabine into the active gemcitabine triphosphate is catalyzed by deoxycytidine kinase, an enzyme that is saturated by 30 minutes. Therefore, enhanced antineoplastic activity requires prolonged infusion times; many physicians during the years 1999 to 2003 studied infusion times ranging from 30 minutes to 24 hours.2-4 Prior studies with 5-FU and with fluorodeoxyuridine demonstrated that individual dosage tolerances were extremely varied, suggesting that studies with dosage escalations according to individual patient tolerance were needed. Capecitabine is an oral prodrug of 5-FU that is designed to exploit the differences in activating enzyme (thymidine phosphorylase) activity between tumor and normal tissue that results in a threefold increase in the concentration of the active metabolite in the tumor cell.6 It was generally recognized that the useful chemotherapy drugs available are gemcitabine, 5-FU, oxaliplatin, bevacizumab, nab-paclitaxel, and recently the experimental nanosomal irinotecan MM-398. With few drugs available, the opportunities for development of combination chemotherapy are limited and cures are unlikely. Further development of new drugs for patients is anxiously awaited. Table 1 shows the reported OS in the literature. Abstract" @default.
- W830986802 created "2016-06-24" @default.
- W830986802 creator A5085544047 @default.
- W830986802 date "2014-12-01" @default.
- W830986802 modified "2023-09-23" @default.
- W830986802 title "Gemcitabine and Capecitabine for Advanced Adenocarcinoma of the Pancreas" @default.
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