A PHASE-II STUDY OF CI-973 LATO(2-)](2-METHYL-1,4-BUTANEDIAMINE-N,N')PLATINUM IN PATIENTS WITH REFRACTORY ADVANCED BREAST-CANCER

CI-973 is a water-soluble platinum diamine complex whose antitumor act ivity is greater than that of cisplatin in some murine tumors. It has shown activity against cisplatin-resistant tumors. This phase II trial had the objectives of determining the therapeutic efficacy of CI-973 in patients with metastatic breast cancer who had been treated with on e prior chemotherapy regimen, and of further defining the toxicity of the agent and the reversibility of its toxicity. CI-973 was administer ed as an intravenous infusion over 30 min with no prehydration or anti emetic programs. Treatment cycles were repeated at 21-day intervals. P atients with histologically confirmed metastatic breast cancer, measur able disease, and good performance status who had received only one pr ior chemotherapy regimen for metastatic disease were eligible for trea tment. Adequate hematologic, renal, and hepatic function were required . A total of 26 patients received a median of two courses of CI-973 (r ange, 1-18 courses). Hematologic toxicity was severe: nearly all patie nts experienced granulecytopenia with granulocyte counts of 0 at all d ose levels. Nevertheless, neutropenic fever and documented systemic in fection were uncommon, and there were no hospitalizations for neutrope nic fever or infection. Visceral disease dominated in this patient gro up. Of the 26 patients, 14 had visceral disease, 6 had bone or bone ma rrow disease, and 6 had skin, soft-tissue, or lymphnode disease. Of th e 26 patients treated, 25 were evaluable for response. There were two partial remissions, one in liver and one in bone, and three minor resp onses, for a response rate of 8%. Nonhematologic toxic effects were mi ld and consisted of nausea and vomiting, fatigue, minimum peripheral p aresthesia, and hypomagnesemia. Further study of CI-973 at the dose an d schedule used in this study is not warranted. Because this agent had no significant extramedullary toxicity, intensification of the dose o f CI-973 with concomitant administration of colony-stimulating factors has the potential to improve response in this patient population.