PO53 CLINICAL IMPACT OF METRONOMIC ORAL COMBINATION CHEMOTHERAPY WITH CAPECITABINE AND CYCLOPHOSPHAMIDE IN PATIENTS WITH METASTATIC BREAST CANCER

Abstract

Background: Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased due to patients’ preference for oral therapy over intravenous (IV) therapy. However, although the quality of life is better with oral therapy, patients are generally unwilling to sacrifice efficacy when prioritizing oral over IV therapy. Capecitabine (X) and cyclophosphamide (C) can be orally administered and have synergistic effects with non-overlapping toxicities in patients with MBC. Clinically, we have observed heavily pretreated patients with MBC with excellent efficacy with XC therapy and less toxicity. In this study, we retrospectively evaluated the efficacy and safety of an oral combination of XC therapy. Methods: A retrospective review was conducted of human epidermal growth factor receptor (HER)2-negative patients with MBC who received XC therapy at Hiroshima City Hiroshima Citizens Hospital; adverse events, time to progression (TTP), and overall survival (OS) were used to evaluate the clinical response to XC therapy. Doses of X and C were determined according to the phase I results from the Kyushu Breast Cancer Study Group (Ohno S et al. Anticancer Research, 2007). A dose of 1657 mg/m2/day capecitabine and 65 mg/m2/day cyclophosphamide was given orally twice daily for 14 days. The treatment was repeated at 3-week intervals until disease progression or treatment interruption due to adverse events. Results: Between 2009 and 2015, we analyzed 71 patients with MBC (median age, 56; range, 27–85 years), with a median previous chemotherapy regimen (range, 0–7). The overall response rate was 40.3%; the response rate (RR) was 41.2% in hormone receptor (HR)positive cancers and 35.0% in HR-negative cancers. The median TTP was 273 days [95% confidence interval (CI), 224–363 days) and median OS was 1045 days (95% CI, 665–1749 days). The median TTP was 197 days in patients who required extended interval or dose reduction and 326 days in patients on standard treatment regimes (p = 0.0047). Further, median TTP was 197 days in patients who suffered from hand-foot syndrome (HFS), whereas 284 days in patients without HFS (p = 0.0362). Grade 3 or 4 leukopenia was observed in 12 cases (16.9%), neutropenia in 10 (14.1%), anemia in 3 (4.2%), and thrombocytopenia in 0 cases (0%). Non-hematological toxicities were mild. HFS was observed in 14 cases (19.7%), although no cases of grade 4 HFS occurred. Only two patients with grade 3 hemorrhagic cystitis interrupted therapy due to adverse events (cyclophosphamide side-effects). Conclusion: Oral XC therapy was very effective with less toxicity in HER2-negative MBC. XC therapy may be a promising oral chemotherapy regime in light of its cost-effectiveness, quality of life, and preference of patients with MBC.