CYCLOPHOSPHAMIDE, MITOXANTRONE AND FLUOROURACIL VERSUS CYCLOPHOSPHAMIDE, MITOXANTRONE AND FLUOROURACIL PLUS LONIDAMINE FOR THE TREATMENT OF ADVANCED BREAST-CANCER - A MULTICENTRIC RANDOMIZED CLINICAL-TRIAL

Lonidamine (LND), a non conventional antineoplastic drug, is a biomodulating agent demonstrating a synergistic effect with cytotoxic drugs such as alkylating agents and anthracyclines. From July 1990 to May 1993, 206 patients with advanced breast cancer were studied to verify if LND plus CNF (cyclophosphamide, novantrone, fluorouracil) was able to enhance CNF activity with regard to response rate, time to progression and survival. After stratification, patients were randomized to receive CNF alone (group A) or CNF plus LND (450 mg orally 3 times a day) (group B). After 8 cycles, patients showing complete or partial response stopped treatment, and patients of group B continued to receive LND alone until disease progression. Overall response rate was 48% in group B versus 39% in group A (p=0.26). Although this difference was not statistically significant, more complete responses (CR) were observed in the LND treated group, especially in patients with soft tissue lesions, (CR rate: 47% versus 21%, respectively) and time to progression was significantly longer, suggesting that LND is able to prolong response duration. Conversely, no differences were observed with regard to overall survival.