Effective salvage therapy with carboplatin/mitomycin C in metastatic breast cancer

Alternative and effective drug regimens in patients with metastatic breast cancer progressing after adriamycin- and taxoid-containing regimens are urgently needed.

In a phase II trial, 43 heavily pretreated patients with metastatic breast cancer were treated with both carboplatin 200 mg/m(2) i.v. and mitomycin C 10 mg/m(2) i.v. on day 1 every 4 weeks. In case of granulocytopenia or thrombocytopenia below grade 3 according to NCI-CTC, the carboplatin dosage was escalated to 300, 400, and 450 mg/m(2) in the next treatment cycle.

During the first 3 cycles the dose intensity of carboplatin could be increased from a mean of 50 to 74 mg/m(2)/week. Beyond this value the carboplatin dose intensity decreased because of hematotoxicity. Based on an intention-to-treat analysis, 9 of 43 patients responded to therapy (21%; 95% CI = 10.04-36.04) including 2 complete and 7 partial responses. 15 patients had no change, 13 progressed, and 6 patients were considered nonevaluable. The median time to progression was 3 (range 0-12) months. NCI-CTC grade 3 or 4 granulocytopenia was observed in 14 patients, grade 3 or 4 thrombocytopenia occurred in 32, grade 3 infections in 3, grade 3 hemorrhage in 1, and grade 3 cardiac dysrhythmias in 1 of the patients.

In anthracycline/ taxoid-pretreated patients, salvage treatment with a combination of carboplatin and mitomycin C seems to be effective and associated with foreseeable toxicity. Based on our results with an intraindividual dose escalation of carboplatin, a dosage of 300 mg/m(2) in combination with mitomycin C 10 mg/m(2) every 4 weeks seems to represent a recommendable starting dose for future studies.