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ONE HUNDRED EIGHTEEN PATIENTS with metastatic carcinoid tumor were randomized to treatment with streptozotocin combined with cyclophosphamide or with 5-fluorouracil (5-FU). Commonly experienced side effects were nausea, vomiting, leukopenia, thrombocytopenia, and nephrotoxicity. Objective response rates among eligible and evaluable patients treated with the 5-FU combination was 14 of 42 (33%) and with the cyclophosphamide combination, 12 of 47 (26%). Among those patients with carcinoids primary to the small bowel the respective response rates were 44% and 37%. The overall response rates for patients with carcinoids of pulmonary or unknown origin were only 12% and 17%. There was no significant difference in patient survival between the two treatment arms. Among 11 patients who received crossover therapy with 5-FU alone there were two responders. There were no responders among eight patients treated with cyclophosphamide alone.Urinary 5HIAA excretion proved to be a useful biologic marker in these patients that correlated well with the observed measurements of tumor bulk.Median survival times from the diagnosis of unresectable malignant disease related to sites of origin of carcinoid tumor were the following; small bowel, 28.4 months; pancreas, 24.0 months; lung, 15.1 months; and unknown origin, 9.0 months.Metastatic carcinoid tumor is a malignant disease susceptible to chemotherapeutic approaches and continued investigation of the therapy of these neoplasms should be strongly encouraged.