Mitomycin C and capecitabine combination (MiXe) in heavily pretreated metastatic breast cancer patients. A dose-finding study

Background: No standard chemotherapy has been defined for metastatic breast cancer patients pretreated with anthracyclines and taxanes. In preclinical studies, mitomycin C (MMC) and capecitabine showed a synergistic effect by upregulation of thymidine phosphorylase, and both drugs were active against breast cancer with a lack of overlapping toxicity, making their combination a well-tolerated regimen. Patients and Methods: A dose-finding study was earned out in order to determine the maximum tolerable dose of MMC combined with fixed-dose capecitabine and to describe the dose-limiting toxicities. Results: Twenty-one patients were enrolled, with metastatic breast cancer pretreated at least with anthracyclines and taxanes (3 at dose level I, 15 at dose level II, 3 at dose level III). At dose level III (MMC 12 mg/m ² and capecitabine 1000 mg/m ² days 2-15) dose-limiting toxicities were recorded in 2 patients (G4 thrombocytopenia, neutropenic fever, G4 neutropenia); dose level II (MMC 10 mg/m ² and capecitabine 1000 mg/m ² days 2-15) was extended for a better safety evaluation. No severe toxicity was noted at this dose level, and therefore this dose was recommend for the phase II study. With regard to activity, 4 partial responses and 2 stable diseases (28%) were recorded. Conclusion: Our data show that the combination is feasible, well tolerated and active in this set of patients.