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.

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/m(2) administered by FDR (10 mg/m(2)/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/m(2) 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/m(2) plus capecitabine 1000 mg/m(2) 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.

• Authors: Andrew H Ko, Anne M Espinoza, Kimberly A Jones, Alan P Venook, Emily K Bergsland, Robin K Kelley, Elizabeth Dito, Anna Ong, Cherry S Hanover, Fergus V Coakley, Margaret A Tempero
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 35 Issue 5 Pg. 411-7 (Oct 2012) ISSN: 1537-453X [Electronic] United States
• PMID: 21552099 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxycytidine
• Capecitabine
• Fluorouracil
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biliary Tract Neoplasms (drug therapy, mortality, secondary)
• Capecitabine
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Follow-Up Studies
• Humans
• Lymphatic Metastasis
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Pancreatic Neoplasms (drug therapy, mortality, secondary)
• Survival Rate
• Treatment Outcome
• Gemcitabine