A Phase I Study of Oral Fluoropyrimidine Capecitabine (Xeloda Roche) Combined With Intravenous Cisplatin in Patients With Advanced Cancer of the Digestive System

OBJECTIVES:

• Determine the dose-limiting toxicity, maximum tolerated dose, and the recommended phase II dose of capecitabine and cisplatin in patients with locally advanced or metastatic cancer of the upper gastrointestinal tract (GI), head and neck, lung, breast, or carcinoma of unknown primary.
• Determine the toxic effects of this regimen in these patients.
• Evaluate possible antitumor effectiveness of this regimen in these patients.
• Determine the toxic effects of cisplatin and capecitabine at the recommended phase II dose in patients with cancer of the upper GI tract.
• Determine the overall survival, time to progression, and duration of response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of capecitabine.

Patients receive oral capecitabine twice daily for 5, 10, or 14 days. Patients also receive cisplatin IV on day 1 of each course. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). The recommended phase II dose is defined as the dose preceding the MTD, provided no more than 3 of 12 patients experience DLT at that dose. Twenty additional patients with cancer of the upper gastrointestinal tract receive treatment with cisplatin and capecitabine at the recommended phase II dose for at least 6 months in the absence of disease progression or unacceptable toxicity.