Lonidamine in High-Risk Breast Cancer Patients

Lonidamine revealed synergistic effects with anthracyclines and alkylating agents in experimental investigations. It differs from conventional cytostatics by acting on the cell energy metabolism and also lacks their typical side effects; therefore it may be valuable to be combined with established chemotherapeutic regimens. Because in unselected patients the results of randomized studies may be influenced by differences in type and combination of prognostic factors, we defined strict entry criteria: no previous systemic palliative treatment, disease-free interval I 2 years, measurable visceral metastases, number of tumor sites ~2, no brain or bone metastases, World Health Organization performance status ~2, age S56. In an ongoing radomized study we are analyzing the remission rate, remission duration, time to treatment failure, and survival time in patients treated with vindesin 3 mg/m2 plus epirubicin 100 mg/mt plus cyclophosphamide 600 mg/m2 (day 1, intravenous, repeated every 3 weeks) ? lonidamine 600 mg/day orally. Eight of 12 patients achieved an objective remission (complete response 4, partial response 4). 1 patient had a stable disease, 2 patients experienced tumor progression; 1 patient is not yet evaluable for response. In spite of the intensity of the therapy no treatment interval prolongation was necessary. Main toxicities were myelosuppression, nausea, emesis, alopecia, and in patients treated with lonidamine, mild myalgia. The addition of lonidamine to polychemotherapy did not affect myelosuppression. Differences in remission rates or remission duration due to lonidamine could not yet be demonstrated. Copyright o 1991 by W.B. Saunders Company