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.