Dosage of capecitabine and cyclophosphamide combination therapy in patients with metastatic breast cancer

Background: Capecitabine is a highly effective and well-tolerated treatment for metastatic breast cancer (MBC) and extends survival when combined with docetaxel. Capecitabine and cyclophosphamide are orally administered and have preclinical synergy and non-overlapping toxicities. Patients and Methods: Sixteen pretreated MBC patients received escalating doses of oral capecitabine 628 to 829 mg/m(2) twice daily (bid) plus oral cyclophosphamide 33 to 50 mg/m(2) bid, on days 1 to 14 every 21 days. Results: Among the ten patients receiving capecitabine/cyclophosphamide 33 to 50 mg/m(2) bid on days 1 to 14, two experienced dose-limiting toxicities (DLT, treatment delay > 1 week due to grade 2 leukopenia). Because neither patient developed further grade > 1 toxicity and none of the patients experienced grade 3/4 toxicities or further DLTs, this dose level is the recommended regimen, producing partial responses in two of five evaluable patients. Conclusion: The recommended all oral capecitabine/cyclophosphamide combination regimen is well tolerated and active in MBC, and is being evaluated in a phase II study in anthracycline-pretreated MBC.