CLINICAL MODULATION OF EPIRUBICIN RESISTANCE BY LONIDAMINE IN PATIENTS WITH ADVANCED SOFT-TISSUE SARCOMAS

To determine if lonidamine (LND) could reverse anthracycline resistanc e In patients with advanced, soft-tissue sarcomas, thirty-six patients were treated with epirubicin (EPI) 120 mg/m(2) i.v. every 3 weeks. Pr ogressive patients were given the same chemotherapy regimen on day 4 i n combination with oral LND, 150 mg on day 1, 300 mg on day 2, and 450 mg on days 3 to 5. Among 35 evaluable patients there were 2 complete responses and 3 partial responses (PR) for an overall response rate of 14%. In the group treated with EPI+LND (24 evaluable patients) 2 PR w ere observed, lasting 3 and 10 months respectively. The overall surviv all was 11.5 months. The most common side-effects were myelotoxicity, nausea and vomiting. Clinical cardiotoxicity was. not observed. Only i n one patient a >20% decrease in LVEF from baseline was recorded. LND related toxicities were mild to moderate myalgia and photophobia. In a pharmacokinetic study performed parallel to the clinical study, no di fference was observed between the parameters derived from EPI and EPILND curves except for Vapp. This study indicates that LND may circumve nt clinical resistance in some cases without altering chemotherapy rel ated toxicity.