Combination of Epirubicin and Lonidamine for Treatment of Advanced Breast Cancer

Abstract

In vitro and in vivo studies have shown that lonidamine potentiates the cytotoxic effect of anthracyclines in simultaneous and sequential combination. On the basis of such evidence, we evaluated the activity and toxicity of a combination of epirubicin plus lonidamine in advanced breast cancer. Between January 1991 and November 1993, 33 patients with advanced breast cancer, age < 75 years and PS < 2, were treated with epirubicin (75 mg/m2 i.v. on day 1, every 3 weeks), plus lonidamine (450 mg/day orally from day 1 continuously until disease progression). Thirty patients were evaluable for response: 4 achieved complete response (13%) and 8 partial response (27%) (total response rate = 40%), 6 (20%) had stabilization of disease, and 12 (40%) progression of disease. The median duration of response was 10 months (range, 4-24+ months). This scheme was tolerated, with a mild additional toxicity related to lonidamine: only WHO grade III myalgia in 1 patient (3%) and epigastralgia in 3 patients (9%). Although some patients seem to have benefited from the combination at the dose levels of the drug used in the study, the therapeutic advantages of addition of lonidamine remain unclear.