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Malignant pheochromocytomas have exhibited partial responses to treatments with 131-I metaiodobenzylguanidine (MIBG) and with chemotherapy. The authors combined these two therapeutic methods to determine if beneficial effects from each would be additive. Patients with documented malignant pheochromocytomas were recruited with the intent of administering 131-I MIBG in three substantial amounts of radioactivity at 3-month intervals followed by a year of chemotherapy in which cyclophosphamide, dacarbazine, and vincristine were to be given in 21-day cycles. Six patients entered the protocol. After the 131-I MIBG treatments, three patients manifested declines in the presence of tumor (smaller tumor volume or abnormalities on bone and 131-I MIBG scans) and the function of tumor (decreased rate of normetanephrine excretion as the major index). Two patients completed at least 9 months of chemotherapy and showed further reductions in the presence and function of tumors and were classified as having partial responses. Progressive disease afflicted three of the other four subjects. Even though toxicity was minimal from 131-I MIBG, it was sufficient to force reduction in the dosages or duration of chemotherapy. A combination of 131-I MIBG treatments and chemotherapy produced additive effects in reducing malignant pheochromocytomas. Toxicity moderately curtailed the proposed chemotherapy protocol.

Twenty-nine evaluable patients with colorectal adenocarcinoma were treated in a phase I-II trial of combination chemotherapy with a 72-h continuous infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU) with an infusion of VP-16 given at 24 and 48 h after the start of therapy. There were five (17 +/- 14%) partial responses lasting 2-6 months (median, 3). Three of these responses occurred among the 10 previously untreated patients. The toxicity of this regimen was pronounced. Four of eight patients with severe neutropenia required hospitalization for infections, two of which were life-threatening; one of six patients with severe thrombocytopenia had a life-threatening hemorrhagic complication; and four patients experienced severe, dose-limiting fatigue. These complications occurred principally with CDDP and VP-16 at doses above 27.5 mg/m2/day and 110 mg/m2/dose, respectively. Mucositis occurred in six patients and limited the dose of 5-FU to 1,300 mg/m2/day. Although the response rate appeared to be high in previously untreated patients, the minimal palliative benefit of treatment and the brief duration of the responses do not compensate for the toxicity observed.