Abstract P6-11-10: Full-Oral, Metronomic Schedule of Vinorelbine (VNB) and Capecitabine (CAPE) in Locally Advanced or Metastatic Breast Cancer (BC) Patients (Pts): A Single Institution, Dose-Finding Study

BACKGROUND: Choice of chemotherapy is a major problem in locally advanced (LABC) or metastatic BC pts already treated with anthracyclines and taxanes, or not suitable for these drugs. VNB and CAPE are two valid options, both tested as single agents or in combination in this setting of pts. Different studies have demonstrated that the metronomic treatment could achieve a significant rate of clinical response with an acceptable toxicity profile. Based on the results of metronomic Phase I/II trial, which fixed the dose of VNB at 60 mg/tot thrice a week and considering that the two drugs have a different safety profile, we designed a dose-finding study, aiming to determine the optimal dose of oral VNB in combination with CAPE, both administered in a metronomic way. PATIENTS AND METHODS: Fixed dose of CAPE was 500 mg thrice a day, continuously. Level I dose of VNB was 20 mg/tot, three times a week for 3 weeks (1 cycle); subsequent cohorts started with 30 mg/tot Level II), 40 mg/tot (Level III) and 50 mg/tot (Level IV), respectively, if no Grade 3-4 toxicity was observed in the same dose level of the previous cohort. Results: Twelve consecutive pts were enrolled. Median age was 67.5 years (49-81), 4 pts were LABC or metastatic at diagnosis, HR status was positive in 11/12 pts (91.6%), 2 pts were HER2+ but could not or no longer receive antiHER2 agents due to cardiac failure. All pts but 2 (83.3%) received anthracyclines, taxanes or both. Mean number of metastatic sites was 3 (1-5). At the 50 mg level of dose, 1 pt developed G3 neurological toxicity during the 3rd week of cycle 1 and 1 pt G4 neutropenia in the 2nd week of cycle 2. No pts treated with the 40 mg level of dose experienced G3 toxicity. The Maximum Tolerated Dose (MTD) was fixed at 40 mg thrice a week. CONCLUSION: MTD of metronomic full-oral schedule of VNB in combination with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the further ongoing Phase II study. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-10.