Phase II study of gemcitabine plus cisplatin in patients with metastatic breast cancer: A north central cancer treatment group trial

Background: This 2-stage, phase II cooperative group trial examined the efficacy and toxicity of 1000 mg/m² gemcitabine plus 25 mg/m ² cisplatin weekly for 3 weeks and repeated every 28 days for patients with previously treated metastatic breast cancer. Methods: Eligible patients had to have measurable metastatic disease. Progression on prior treatment with at least 1 chemotherapy program for metastatic disease and 1 prior anthracycline and/or taxane-containing regimen in either the metastatic or adjuvant setting was required. Patients who had received more than 2 chemotherapy treatments were not eligible for this study. Results: Fifty-eight eligible patients were entered on this 2-stage study. A 38% incidence of grade 4 thrombocytopenia observed in the first stage of accrual required lowering the chemotherapy doses to 800 mg/m² gemcitabine plus 20 mg/m² cisplatin weekly for the first 3 weeks of a 4-week cycle during the second stage of the study. The overall response rate was 29% (95% confidence interval [CI], 11-52%) among patients receiving the original study dose and 32% (95% CI, 18-50%) for patients receiving the lower dose. In the original- and lower-dose groups, median time to progression was 30.7 weeks (95% CI, 12.7-43.4 weeks) and 26.0 weeks (95% CI, 19.0-32.1 week), respectively. Median survival of the original- and low-dose groups was 67.9 weeks (95% CI, 42.3-90.6 weeks) and 54.1 weeks (95% CI, 41.6-73.6 weeks), respectively. Hematologic toxicities were more manageable in the lower-dose group, whereas the nonhematologic toxicity profile was similar in the 2 dose groups. Conclusions: The response rate of this combination of gemcitabine and cisplatin is similar to that reported by other investigators but may not differ substantially from reports with single-agent gemcitabine in this patient population. The original dose level we used had unacceptable toxicity, which required lowering the doses of both gemcitabine and cisplatin by 20% to achieve acceptable toxicity and preserve clinical activity.