A phase II study of topotecan administered five times daily in patients with advanced gastric cancer.

Overview

OBJECTIVE: Topotecan (Tpt), a semisynthetic analogue of camptothecin (Cpt), has shown excellent preclinical activity in a number of solid tumors. Cpt, the parent compound, has preclinical activity against several gastrointestinal tumors, including a gastric adenocarcinoma xenograft. A phase-II clinical trial was conducted to assess the activity to Tpt in patients with advanced gastric cancer. MATERIALS AND METHODS: 15 patients with advanced, incurable gastric adenocarcinomas were treated. Tpt 1.5 (mg/m2/day) was administered intravenously as a 30-min infusion daily for 5 consecutive days. Treatments were repeated on a 21-days cycle. RESULTS: No major objective responses were observed in 13 evaluable patients (response rate = 0%; 95% confidence interval = 0-22%). The major dose-limiting toxicity in this trial was myelosuppression, which was severe in this patient population. CONCLUSIONS: Tpt at the dose and schedule studies does not possess substantial antitumor activity in patient with gastric cancer, and the toxicities were formidable. We do not advocate further development of this drug in the treatment of gastric cancer. Tpt has shown more promising activity and tolerability in other patient populations, and these areas deserve further exploration.