CISPLATIN AND EPIRUBICIN PLUS ORAL LONIDAMINE AS FIRST-LINE TREATMENTFOR METASTATIC BREAST-CANCER - A PHASE-II STUDY OF THE SOUTHERN ITALYONCOLOGY GROUP (GOIM)

Lonidamine (LND) is a unique antineoplastic drug derived from indazole -3-carboxylic acid which inhibits oxygen consumption and aerobic glyco lysis, interfering with energy metabolism of neoplastic cells. LND has been experimentally shown to potentiate the cytotoxic effects of epir ubicin (EPI) in human breast cancer cell lines, cisplatin activity in both platinum-sensitive and -resistant human ovarian carcinoma cell li nes, and EPI antineoplastic activity in some recent phase III trials c arried out in advanced breast cancer. A multicenter phase II trial was carried out with the combination of cisplatin 60 mg/m(2), EPI 100 mg/ m(2) and LND 450 mg/day p.o. in three refracted doses/day starting 2 d ays before cisplatin and EPI (day -2 and -1), stopping 2 days after ch emotherapy (day 0, +1 and +2). Thirty patients with metastatic breast cancer were enrolled into the study. Twenty-nine patients were evaluab le for objective response. The overall response rate accordingly to an intent-to-treat analysis was 73% (95% CL 54-88%). Four patients achie ved complete response (13%; 95% CL 4-31%) with a median duration of 9. 5 months (range 4-16) and 18 patients had partial response (60%; 95% C L 41-77%) with a median duration of 9.8 months. Stable disease was obt ained in five cases (17%) and progressive disease was recorded in thre e patients. One patient died of progressive cancer before restaging. T he overall median survival of the whole series of patients was 14+ mon ths. The most frequent toxicities were represented by gastrointestinal and hematological side effects. The combination of cisplatin + EPI pl us oral LND is active against metastatic breast carcinoma. The antineo plastic activity of the cisplatin + EPI + LND regimen is as high as th at reported for more aggressive regimens such as the fluorouracil + do xorubicin + cyclophosphamide combinations without an increase in toxic effects.