Phase II trial of carboplatin and etoposide in metastatic breast cancer

High-dose chemotherapy with hematopoietic support produces high rates of response in metastatic breast cancer. To facilitate new high-dose regimens there is a need to identify active agents with toxicity limited to hematopoietic suppression. Cisplatin/etoposide is a highly active regimen in metastatic breast cancer, but cisplatin dose-escalation is limited by nonhematologic toxicity. Carboplatin is active in breast cancer and has marrow-dominant toxicity. Demonstration of activity for the combination of carboplatin and etoposide would facilitate their inclusion in high-dose programs.

A single treatment arm prospective Phase II study in patients with measurable or evaluable breast cancer was done.

Forty-six patients with metastatic breast cancer were treated with the combination of carboplatin and etoposide. Among 19 patients without prior chemotherapy, one complete and seven partial responses were observed, for an objective response rate of 42% (95% exact confidence intervals [CI], 20-67%). One partial response was seen among 12 patients with prior chemotherapy limited to the adjuvant setting. No responses were seen among 14 patients who had received prior chemotherapy for metastatic cancer. Two treatment-related deaths occurred, both attributable to sepsis. One patient returned to her community for treatment after receiving one course of protocol therapy before response assessment and could not be studied for response.

The activity observed with this regimen in patients with no prior chemotherapy coupled with its potential for dose escalation suggests a possible role in high-dose programs with hematopoietic support. The inactivity of the combination in patients with prior therapy for metastatic breast cancer indicates that there is no advantage to its use in the salvage setting.