A preliminary study of cyclophosphamide (NSC-26271), adriamycin (NSC-123127), imidazole carboxamide (NSC-45388), and actinomycin D (NSC-3053) with or without MER-BCG in patients with advanced sarcomas

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Abstract
Polychemotherapy for soft tissue sarcomas has been reported to produce response rates ranging from 24-60%. Immunotherapy has reportedly prolonged survival after surgery for some tumors and enhanced the effectiveness of chemotherapy. This report summarizes preliminary experience with the combination of cyclophosphamide, adriamycin, imidazole carboxamide (DTIC) and actinomycin D (CAIA) with or without methanol extraction residue of BCG (MER) in patients with advanced sarcomas. Among 15 patients treated with CAIA + MER, 4 achieved partial regression with a median duration of 3 mo. (leiomyosarcoma, hemangiosarcoma, fibrosarcoma and mesothelioma). Of 14 patients receiving CAIA alone, 2 achieved regression, each for 2 mo. (hemangiosarcoma and hemangiopericytoma). Overall, 6 of 29 (21%) experienced an objective regression. Nausea and vomiting occurred in all patients; stomatitis affected 11 of 29 patients; and the majority of patients developed profound anorexia and generalized debility. The subsequent inanition and cachexia often compromised attempts to complete the intended treatment regimen. Eighteen of 29 patients had leukocyte counts < 3000 cells/mm3; 4 had leukocyte counts < 1500 cells/mm3. One-third had platelet counts < 100,000 cells/mm3, but significant hemorrhage was rare. No cardiomyopathy was observed after adriamycin, but no patient received > 450 mg/m2 total dose. MER toxicity included local skin reactions which ranged from erythematous papules through necrotic draining ulcers up to 2 cm in diameter. Although there was some increase in lymphocyte responsiveness to PHA [phytohemagglutining] and Con A [concanavalin A] in patients receiving MER, analysis of variance by nonparametric techniques showed no statistically significant differences in pretreatment or follow-up immune studies for patients receiving CAIA alone or CAIA + MER. Because of small numbers it is not possible to make a precise comparison of the 2 treatment regimens, but there was clearly no substantial therapeutic advantage achieved by adding MER. The magnitude of treatment-related toxicity and meager response rates would preclude the regular use of either these regimens.