FEC (FLUOROURACIL, EPIRUBICIN AND CYCLOPHOSPHAMIDE) VERSUS EM (EPIRUBICIN AND MITOMYCIN-C) WITH OR WITHOUT LONIDAMINE AS FIRST LINE TREATMENT FOR ADVANCE BREAST-CANCER - A MULTICENTRIC RANDOMIZED STUDY - PRELIMINARY-REPORT

In experimental models, both in vivo and in vitro, and in clinical stu dies, lonidamine demonstrated a synergistic activity with anthracyclin es and increased their cytotoxicity. In a randomized clinical trial tw o different epirubicin containing regimens (epirubicin (E), 75 mg/m(2) every three weeks and mitomycin-C (M), 10 mg/m(2) every six weeks. FE C: fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2) and cyclophosphamid e 500 mg/m(2) every three weeks) were compared with or without the add ition of lonidamine (L) as first line treatment for patients with adva nced breast cancer. Lonidamine was given orally at a dosage of 600 mg/ day. Patients were randomly allocated to receive FEC, EM, FECL or EML. A factorial two by two design was followed to analyze the results (FE C/FECL versus EM/EML and FEC/EM versus FECL/EML). EM regimen showed a higher activity than FEC (CR+PR: EM/EML 76.4%, FEC/FECL 60%). A higher response rate was observed in the patients receiving lonidamine with respect to those not receiving this drug (CR+PR: FECL/EML 76.2%, FEC/E M 61.4%). Median time to progression was longer in the group submitted to EM chemotherapy (EM/EML: 302 days, FEC/FECL: 237 days) and in the patients receiving lonidamine (FECL/EML: 320 days, FEC/EM: 266 days). These preliminary results suggest that EM combination is highly active against breast cancer and that the addition of lonidamine to anthracy cline containing regimens can increase their activity.