A phase II study of CI-973 [SP-4-3(R)]- [1, 1-cyclobutane-dicarboxylato (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 activity 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 one prior chemotherapy regimen, and of further defining the toxicity of the agent and the reversibility of its toxicity. CI-973 was administered as an intravenous infusion over 30 min with no prehydration or antiemetic programs. Treatment cycles were repeated at 21-day intervals. Patients with histologically confirmed metastatic breast cancer, measurable disease, and good performance status who had received only one prior chemotherapy regimen for metastatic disease were eligible for treatment. Adequate hematologic, renal, and hepatic function were required. A total of 26 patients received a median of two courses of CI-973 (range, 1–18 courses). Hematologic toxicity was severe: nearly all patients experienced granulocytopenia with granulocyte counts of 0 at all dose levels. Nevertheless, neutropenic fever and documented systemic infection were uncommon, and there were no hospitalizations for neutropenic fever or infection. Visceral disease dominated in this patient group. Of the 26 patients, 14 had visceral disease, 6 had bone or bone marrow disease, and 6 had skin, soft-tissue, or lymph-node disease. Of the 26 patients treated, 25 were evaluable for response. There were two partial remissions, one in liver and one in bone, and three minor responses, for a response rate of 8%. Nonhematologic toxic effects were mild and consisted of nausea and vomiting, fatigue, minimum peripheral paresthesia, and hypomagnesemia. Further study of CI-973 at the dose and schedule used in this study is not warranted. Because this agent had no significant extramedullary toxicity, intensification of the dose of CI-973 with concomitant administration of colony-stimulating factors has the potential to improve response in this patient population.