PHASE-II TRIAL OF CHLOROZOTOCIN AND FLUOROURACIL IN ISLET CELL-CARCINOMA - A SOUTHWEST ONCOLOGY GROUP-STUDY

Purpose: A phase II trial that used fluorouracil (5-FU) and chlorozotocin (CTZ) was performed in patients with metastatic islet cell carcinoma to determine the response rate and toxicity. Patients and Methods: Patients received four cycles of induction chemotherapy. Good-risk patients received 5-FU 800 mg/m2/d days 1 to 4 as a continuous intravenous (IV) infusion (CIV) and CTZ 175 mg/m2 IV on day 1. Poor-risk patients (previous radiation to ≥ 25% bone marrow-bearing areas; serum bilirubin ≥ 5 mg/dL; creatinine > 1.0 mg/dL) received 5-FU 600 mg/m2/d and CTZ 75 mg/m2 in a similar manner. In responding or stable patients, reduced doses of 5-FU and CTZ were continued as maintenance therapy (maximum, 18 months). Results: Forty-seven of 51 patients were eligible, and 44 received chemotherapy. Fourteen of 44 patients had partial responses, with 13 of 36 (36%; 95% confidence interval [CI], 21.0% to 54.0%) good-risk patients and one of eight (12%; 95% CI, 0.3 to 52.6%) poor-risk patients responding. Median survival of all patients was 25 months, and the median response duration was 11 months. Side effects were moderate to severe and included myelosuppression and gastrointestinal toxicity. Thirteen patients developed renal toxicity, which was severe or life-threatening in five. This seemed to be related to the administration of cumulative doses of CTZ ≥ 1,500 mg. Conclusion: These results demonstrate that the combination of 5-FU and CTZ has activity in islet cell carcinoma, but the occurrence of renal toxicity secondary to CTZ may limit the use of this agent. © 1992 by American Society of Clinical Oncology.