Clinical antitumor activity and toxicity of streptozotocin (NSC-85998)

Abstract

Streptozotocin was administered to 106 patients with advanced malignancies. Therapeutic responses were observed in Hodgkin's disease, 7/16, lymphocytic lymphoma, 3/11, Burkitt's lymphoma, 1/12, and acute lymphocytic leukemia, 1/5. Two of 7 patients with islet cell carcinoma, 1 insulin-secreting and 1 serotonin-secreting, responded, but 8 patients with malignant carcinoid tumors originating from the ileum failed to demonstrate a reduction in either urinary 5-hydroxyindole acetic acid or tumor mass. Additional evidence of drug activity was observed in 2 patients with melanoma and 1 of 8 cases with sarcoma. There was no apparent cross resistance between Streptozotocin, a methyl nitrosourea, and BCNU, a chloroethyl nitrosourea. Hematologic toxicity was observed in 9% of cases, whereas renal damage demonstrated in 28% was the principal treatment-limiting drug effect. Ten to twenty percent of each total dose is excreted in the urine with an intact N-nitroso group within 2 hours after administration. Recommended maximum doses based on results of these studies are 500 mg/m2 for 5 days or 1.5 g/m2/week in patients with normal renal function.