Mitomycin C and Capecitabine Combination (MiXe) in Heavily Pretreated Metastatic Breast Cancer Patients. A Dose-finding Study

• Published in: Anticancer research 2005-11, Vol.25 (6C), p.4513-4517
• Main Authors: MAISANO, Roberto, CARISTI, Nicola, MARE, Marzia, MAFODDA, Antonino, CARBONI, Rita, MONTALTO, Erika, IORFIDA, Monica, NARDI, Mario
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Capecitabine; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil - analogs & derivatives; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Mitomycin - administration & dosage; Mitomycin - adverse effects; Neoplasm Metastasis; Tumors
• ISSN: 0250-7005; 1791-7530

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 up-regulation 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 carried 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.