Cisplatin with capecitabine: tolerance and activity in a phase I/II study preferentially enrolling patients with...

Capecitabine is an oral prodrug of flurouracil with broad activity against various malignancies. We explored its tolerance and preliminary efficacy when given together with cisplatin in a phase I/II study preferentially enrolling gastric cancer patients.

The study was a 3+3 dose escalation design and at the recommended phase II dose it included an expanded cohort of patients with upper gastrointestinal cancer. The dose of cisplatin was escalated from 40 to 50 mg/m(2) on day 1, and capecitabine of 2,500 mg/m(2)/day starting on day 2, was escalated from 5 days to 10 and then to 14 days, with the cycle repeated every 21 days. Prolonged maintenance with capecitabine was offered to selected patients completing three to six cycles.

A total of 34 patients were enrolled, and 27 patients were also evaluable for response. Dose limiting toxicities were palmar plantar erythrodyesthesia (PPE) and diarrhea; grade 3 and 4 neutropenia occurred in 8.8% and grade 3 PPE in 5.9%, while the most common grade 1-2 toxicities were anemia, neutropenia, fatigue and PPE (11.7% each). There were no treatment related deaths. With cisplatin at 40-50 mg/m(2) day 1 and capecitabine at 2,500 mg/m(2)/day for 5 -14 days every 21 days, 18 patients with gastric cancer were treated and 7 had partial responses.

A regimen of capecitabine and cisplatin at the doses and schedules explored was safe and active in patients with gastric cancer. Moreover, a 6-month administration of adjuvant capecitabine proved feasible, yielding favorable results after treatment completion and surgery, and should be investigated further.