title: Combination chemotherapy for soft-tissue sarcomas: a phase III study.
abstract: A total of 144 patients with advanced sarcomas were entered into a randomized prospective protocol with four treatment arms utilizing different combinations of chemotherapeutic agents. Of these, 120 patients (83%) were judged acceptable. Treatment  1: actinomycin-D (Act-D), 0.01 mg/kg IV, days 1--5; phenylalanine mustard (L-PAM), 4 mg PO, days 1--10 every six weeks. Treatment  2: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, days 1--10; vincristine, 1 mg IV, days 1, 8, 15, 22, 29, 36, repeat every six weeks. Treatment  3: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, DAYS 1--10; NSC-1026, 200 mg/kg IV, days 1--6. Treatment  4: Adriamycin, 0.4 mg/kg IV, days 1, 2, 3, 8, 9, 10, then 2XWK starting day 15 (max. 1,200 mg). There was a provision that upon progression of the disease in the first three treatment regimens, patients would be crossed over to Treatment  4. Responses were as follows:  1 - Partial Response (PR) 1/25; No Change (NC) 9/25 (36%). gF2 - NC 17/26 (65%).  3 - NC 13/25 (52%).  4 - Complete Response (CR) 1/41; PR 6/41; (15%); NC 27/41 (66%). Clearly Treatment  4 was the best arm, with a 17% response rate and an initial progression rate of 17%. The only other response was a partial in  1. The difference is statistically significant (H = 17.247, P = 0.0006). If the responders to Adriamycin were analyzed without crossovers, the response rate would be 22% (6/27). (H =  14.079, P = 0.003). Median times to progression were 12.5, 8.7 weeks for  1 and  2, and 5 weeks for  3 and  4. There was no significant difference in the median survival times among the four treatment arms. It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents.
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic; D003515:Cycloleucine / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D012075:Remission, Spontaneous; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D003515:Cycloleucine; D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin; D008558:Melphalan