Phase II trial of neocarzinostatin in patients with bladder and prostatic cancer: toxicity of a five-day iv bolus schedule.

Neocarzinostatin (NCZ), a new antitumor antibiotic, was administered to 19 patients with bladder cancer, 16 patients with prostatic cancer, and 3 patients with hepatoma. All patients had objectively measurable metastatic lesions including 21 with palpable nodes or subcutaneous nodules, 10 with pulmonary nodules as demonstrated by chest x-ray, 4 with malignant hepatomegaly, and 3 with bidimensional pelvic masses as demonstrated by CT scanning. Sixty-five courses of NCZ were administered via an intravenous bolus daily for five days with dosages ranging from 1500 to 3000 U/m2. Immediate toxicity was not dose-limiting except for 1 episode of anaphylaxis and 1 of acute renal failure. Myelotoxicity was delayed, dose-dependent, noncumulative, and dose-limiting. Thrombocytopenia was prolonged or irreversible in 5 cases. The maximally tolerated dose was 2750 U/m2. One patient with NCZ-associated pulmonary fibrosis and 1 with biopsy-proven hepatitis are discussed in detail. Neocarzinostatin demonstrated minimal therapeutic activity (1 partial remission) in patients with bladder cancer. There was no response in patients with prostatic cancer or hepatoma.