Effects of amphotericin B on combination chemotherapy of metastatic sarcomas

Ninety-four evaluable patients with metastatic soft tissue and bone sarcomas entered into a prospective randomized trial (SEG 78SAR327) to determine whether amphotericin B (AMB), a membrane-permeabilizing and immunopotentiating agent, could increase either the response rates or the survival of patients treated with a three-drug combination chemotherapy regimen consisting of Adriamycin, cyclophosphamide, and methotrexate (ACM). Pretreatment patient characteristics were similar in each arm. In patients treated with ACM there were 4% complete responses and 34% partial responses, compared with only 5% partial responses on ACM + AMB (P less than 0.05). However, there was no difference in the median time to progression (5.0 months on either arm) or in survival (7.0 months on ACM, and 6.0 months on ACM + AMB). Myelosuppression was the dose-limiting toxicity, and was equal in each treatment arm. The addition of AMB to dactinomycin during maintenance therapy did not result in any complete or partial responses. It is concluded that despite definite biologic activity in experimental tumor models, AMB is not useful clinically in potentiating chemotherapeutic drug activity in patients with metastatic sarcomas, and actually results in a decrease in the frequency of objective responses.