LONIDAMINE SIGNIFICANTLY INCREASES THE ACTIVITY OF EPIRUBICIN IN PATIENTS WITH ADVANCED BREAST-CANCER - RESULTS FROM A MULTICENTER PROSPECTIVE RANDOMIZED TRIAL

Purpose: Some evidence in vitro and in vivo shows that lonidamine (LND ) can positively modulate the activity of doxorubicin and epirubicin ( EPI). On this basis, a multicenter prospective randomized trial was pe rformed in patients with advanced breast cancer (BC) to determine if t he addition of LND to EPI could increase the response rate of EPI alon e. Patients and Methods: From May 1991 to May 1993, 207 patients were enrolled onto this study and randomized to receive intravenous (IV) EP I (60 mg/m(2) on days 1 and 2) alone or with LND (600 mg orally daily) . EPI administration was repeated every 21 days until tumor progressio n or for a maximum of eight cycles. LND was administered continuously until chemotherapy withdrawal. Results: Response rate was significantl y superior for the EPI plus LND scheme compared with the single-agent EPI either considering assessable patients (60.0% v 39.8%; P < .01) or including all registered patients according to an intention-to-treat analysis (55.3% v 37.5%; P < .02). The distribution of the response ra te according to the site of disease did not show any significant diffe rence between the treatment arms, except for the patient subgroup with liver metastases in which the combination EPI plus LND resulted in a significant improvement of responses than EPI alone. Toxicity was mode rate, and except for myalgia, no adjunctive side effects were observed in the EPI plus LND arm. Overall survival and time to progression wer e similar in both groups. Conclusion: This study confirms in vivo that the activity of EPI is enhanced by the concomitant LND administration . (C) 1996 by American Society of Clinical Oncology.