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American Journal of Clinical Oncology:
doi: 10.1097/COC.0b013e3182185888
Original Articles: Gastrointestinal

Optimizing the Administration of Fixed-Dose Rate Gemcitabine Plus Capecitabine Using an Alternating-week Schedule: A Dose Finding and Early Efficacy Study in Advanced Pancreatic and Biliary Carcinomas

Ko, Andrew H. MD*; Espinoza, Anne M. MD*; Jones, Kimberly A. MD; Venook, Alan P. MD*; Bergsland, Emily K. MD*; Kelley, Robin K. MD*; Dito, Elizabeth RN*; Ong, Anna RN*; Hanover, Cherry S. RN; Coakley, Fergus V. MD*; Tempero, Margaret A. MD*

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Abstract

Objectives: This multisite study sought to optimize the dosing, schedule, and administration of fixed-dose rate (FDR) gemcitabine plus capecitabine for advanced pancreatic and biliary tract cancers using an alternating-week dose schedule of both agents.

Methods: Patients with previously untreated advanced pancreatic and biliary tract cancers with Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. For the dose-finding portion, a standard 3+3 dose-escalation schema was used, with the gemcitabine dose kept at 1000 mg/m2 administered by FDR (10 mg/m2/min) on day 1 of each 14-day cycle, and capecitabine given on days 1 to 7 at doses ranging from 800 to 1500 mg/m2 twice daily. Primary study objective was determination of maximum tolerated dose (MTD). The cohort at MTD was expanded for further efficacy assessment.

Results: A total of 45 patients (median age 61 y; 93% pancreatic/7% biliary; 84% with metastatic disease) were enrolled. Median number of cycles received was 11.5. The MTD using this dose schedule was FDR gemcitabine 1000 mg/m2 plus capecitabine 1000 mg/m2 bid, due to a high incidence of late hand-foot syndrome observed at the next higher dose level. Most common nonhematologic adverse events related to treatment included nausea/vomiting (overall rate, 64%; all grade 1/2) and hand-foot syndrome (overall rate, 60%; grade 3, 22%). The incidence of grade 3/4 hematologic adverse events was 24%. Six of 41 evaluable patients (14.6%) had a partial response; 18 of 31 patients (58%) with elevated baseline CA 19-9 level had ≥50% biomarker decline during treatment. Estimated median time to tumor progression and overall survival were 5.5 and 9.8 months, respectively (5.5 and 10.1 mo in the metastatic pancreatic cancer cohort).

Conclusions: This dosing schedule of FDR gemcitabine plus capecitabine is active in patients with advanced pancreatobiliary cancers. Given its favorable toxicity profile and convenience, this regimen represents an appropriate front-line option for this patient population and may serve as the foundation on which new investigational agents are added in future trial design.

© 2012 Lippincott Williams & Wilkins, Inc.

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