FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line treatment for advanced breast cancer. A multicentric randomised study. Final results

From May 1991 to December 1996, 326 patients with advanced metastatic breast cancer were enrolled in a multicentre, randomised, phase III clinical trial with four arms. Patients were randomised to receive chemotherapy according to the FEC regimen (5-fluorouracil CS-FU) 500 mg/m(2), epidoxorubicin (EPI) 75 mg/m(2) and cyclophosphamide (CFA) 500 mg/m2, intravenously (i.v.), every 3 weeks) or the EM regimen (EPI 75 mg/m(2), i.v. every 3 weeks; mitomycin C (MMC) 10 mg/m(2), i.v. every 6 weeks) or the same regimens with the addition of lonidamine (LND) until disease progression (orally, thrice daily, 150+ 150 + 300 mg); a maximum of eight chemotherapy cycles were planned. The aim of the trial was 2-fold: to compare the EM regimen with the commonly used FEC regimen and to evaluate the possible role of the addition of LND. Patients were eligible if they had histologically proven breast carcinoma, metastatic or locoregional relapse with measurable and/or evaluable disease and were aged between 18 and 70 years: 318 patients were considered eligible. Patients with previous anthracycline-based adjuvant chemotherapy or those who relapsed within 6 months after any adjuvant chemotherapy regimen were excluded. Chemotherapy-related toxicity of grade greater than or equal to 3 was manageable and then was no significant difference between the arms in terms of haematological side-effects. The impact on heart function was mild. No increased toxicity was observed in the LND arms (apart from myalgias in 27-30% of the cases). A significant increase in the complete response rate was observed for the FEC/EM + LND group (20.4%) Versus the FEC/EM group (10.8%). The median survival time and the median time to progression for the overall series were 608 days and 273 days, respectively; EM+/-LND achieved significantly improved survival and time to progression versus FEC+/-LND (P = 0.01). This result was confirmed also when the analysis was restricted to patients previously treated with adjuvant CMF schedules. On the basis of these results, we conclude that EM may represent a valuable alternative to FEC for patients requiring a first-line regimen for advanced/ metastatic breast carcinoma, especially in patients previously treated with CMF in an adjuvant setting. Furthermore, we conclude that, in spite of a better complete response rate in the LND arms, as there was no clear advantage in time to progression or survival resulting from the addition of LND to the FEC or EM regimens, the routine use of LND is not warranted outside a clinical trial. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.