Can interleukin-2 reverse anthracyclin chemoresistance in metastatic soft tissue sarcoma patients. Results of a prospective phase II clinical trial

Anthracyclin-based chemotherapy is the most efficient chemotherapy for adva nced or metastatic soft tissue sarcoma (STS), Development of anthracyclin c hemoresistance has been widely documented. In a previous clinical trial, we evaluated a possible reversal of anthracyclin chemoresistance after exposu re to subcutaneous IL-2, The current phase II clinical study entered 17 pro ven metastatic STS patients, refractory to anthracyclin chemotherapy, who r eceived IL-2, and subsequent anthracyclin-based chemotherapy, Subcutaneous IL-2 was administered at 18 million Units/day, 5 days a week for two consec utive weeks. Treatment was administered safely at the full dose for 16 out of 17 patients, and toxicity was mild. One patient had treatment stopped be cause of rapidly progressive disease. As soon as patients met biological an d clinical criteria, chemotherapy was administered, The median delay was 12 days (2-23) from the end of IL-2 administration. Only 13 patients received anthracyclin chemotherapy after IL-2, The other 4 patients did not receive chemotherapy for progressive disease. One partial response was observed ou t of 13 evaluable patients (7.7% overall response, 95% confidence interval: 0.2 to 36), The overall response rate was 5.9% (95% CI: 0.15 to 29), so th e study was stopped due to lack of efficacy. In previous and current studie s, a few patients have developed restored anthracyclin chemosensitivity fol lowing exposure to IL-2. No conclusive evidence of IL-2 chemoresistance rev ersal was obtained from this study. Further investigations need to be perfo rmed with perhaps a larger group of more carefully selected patients using a different schedule and sequence of combined cytokines and chemotherapy.