A PHASE-II STUDY OF TOPOTECAN ADMINISTERED 5 TIMES DAILY IN PATIENTS WITH ADVANCED GASTRIC-CANCER

Objective: Topotecan (Tpt), a semisynthetic analogue of camptothecin ( Cpt), has shown excellent preclinical activity in a number of solid tu mors. Cpt, the parent compound, has preclinical activity against sever al gastrointestinal tumors, including a gastric adenocarcinoma xenogra ft. A phase-II clinical trial was conducted to assess the activity of Tpt in patients with advanced gastric cancer. Materials and Methods: 1 5 patients with advanced, incurable gastric adenocarcinomas were treat ed. Tpt 1.5 (mg/m(2)/day) was administered intravenously as a 30-min i nfusion daily for 5 consecutive days. Treatments were repeated on a 21 -day 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 myelosuppressio n, which was severe in this patient population. Conclusions: Tpt at th e dose and schedule studied does not possess substantial antitumor act ivity in patients with gastric cancer, and the toxicities were formida ble. We do not advocate further development of this drug in the treatm ent of gastric cancer. Tpt has shown more promising activity and toler ability in other patient populations, and these areas deserve further exploration.