Phase I trial of bruceantin.

Bruceantin was administered to 33 patients with advanced solid tumors or hematologic neoplasms. The schedule consisted of four weekly iv injections at one dose level followed by a 2-week "no-treatment" period; this program was repeated every 6 weeks. A total of 156 weekly injections were given over a dose range of 0.8-8.5 mg/m2. Systolic and diastolic hypotension was dose-related and dose-limiting at doses of greater than or equal to 6.0 mg/m2. Transient febrile reactions were dose-related. Gastrointestinal toxicity was commonly observed but was not dose-limiting. There was no hematologic or renal toxicity; hepatic toxicity was subclinical and reversible. Of 18 patients evaluable for antitumor response one patient with adenocarcinoma of the cervix experienced a less than 50% disease regression lasting 10 months and one patient with pleural mesothelioma experienced disease stabilization lasting 4 months. A phase II study of bruceantin is recommended at a starting dose of 5.5 mg/m2 weekly for 4 weeks as a 4-hour iv infusion repeated at 6-week intervals.