Phase II trial of neocarzinostatin in patients with bladder and prostatic cancer. Toxicity of a five-day IV bolus schedule

Abstract

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.