Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer

Authors


Abstract

BACKGROUND

The authors performed a dose escalation study of cisplatin and the novel deoxycytidine analog, tezacitabine, to determine the maximum tolerated dose of the combination.

METHODS

Twenty-three patients with advanced cancer and good performance status were accrued to 3 dose levels of tezacitabine (150–270 mg/m2) and cisplatin (50 mg/m2). Using a 28-day treatment cycle, both drugs were administered on Days 1 and 15.

RESULTS

Hematologic toxicity was the most frequently observed side effect and was dose limiting. Grade 3 or 4 neutropenia and thrombocytopenia complicated 75% and 31% of all cycles, respectively. Nonhematologic toxicities were mild. Among 18 evaluable patients, 2 with upper gastrointestinal tract tumors achieved partial responses and 4 had stable disease.

CONCLUSIONS

Based on dose-limiting neutropenia and thrombocytopenia at the highest dose level, the recommended Phase II doses are 200 mg/m2 of tezacitabine and 50 mg/m2 of cisplatin. Cancer 2003;97:1985–90. © 2003 American Cancer Society.

DOI 10.1002/cncr.11273

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