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%). #2 ‐ 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 #l. 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.