An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: a phase II study

Oral administration of cyclophosphamide (CTX) and capecitabine may have a greater potential for treatment of metastatic breast cancer (MBC) due to anti-angiogenesis resulting from the metronomic dosage and upregulation of thymidine phosphorylase by CTX. The purpose of this phase II study was to evaluate the efficacy and safety profile of an all-oral combination of metronomic CTX plus capecitabine for women with anthracycline- and taxane-pretreated MBC. In this prospective single-center, open-label, phase II trial, patients with measurable disease received oral metronomic CTX 65 mg/m(2) daily on days 1-14 plus capecitabine 1,000 mg/m(2) twice daily on days 1-14. The treatment was repeated every 3 weeks, and continued until disease progression, unacceptable toxicity or withdrawal of informed consent. The primary endpoint of the study was time to progression (TTP). A total of 68 patients were enrolled and received 537 cycles of chemotherapy with a median of 8 cycles (range: 1-30 cycles) per patient. Sixty-six patients were evaluated for efficacy with all patients for toxicity. With a median follow-up time of 26 months, the median time to progression was 5.2 months (95% CI, 4.2-6.2 months), and the median overall survival was 16.9 months. The overall response rate was 30.3% (95% CI, 20-43%). Clinical benefit rate was 53.0% (95% CI, 38-62%). The doublet was well tolerable, with anorexia (7.5%), the only grade 3/4 adverse events occurring in more than 5% of patients. Grade 3 hand-foot syndrome was 4.4%. The all-oral combination of metronomic CTX plus capecitabine is an effective and convenient and well-tolerated regimen for MBC. (ClinicalTrials.gov number, NCT00589901).