Dose finding and pharmacokinetic study of an all-oral combination regimen of oral vinorelbine and capecitabine in metastatic breast cancer (MBC) patients: Final results

Abstract

666 Background: The study investigated oral vinorelbine (NBV oral) and Capecitabine (CAP) combination, which offers the convenience of an all-oral regimen. Methods: to determine maximal tolerated dose (MTD), recommended doses (RDs), safety, efficacy of the combination and to investigate potential drug-drug interaction. Forty-four patients (pts) with first (N=35) or second line (N=9) MBC entered the study. Three schedules were tested: NVB oral D1, D8/CAP D1-D14 every 3 weeks, NVB oral weekly/CAP D1-D14 every 3 weeks, and NVB oral D1, D8/CAP D1-D14 every 4 weeks. NVB oral was given at 60 mg/m2 or 80 mg/m2 with CAP from 1650 to 2500 mg/m2/d. Results: Median age 53.6 y (range; 31.6–73.8), 29 pts (65.9%) received prior (neo)adjuvant CT, 34 pts (77.3%) had visceral involvement and 29 pts (65.9%) had ≥ 2 organs involved. DLTs consisted in neutropenia resulting in delay in starting cycle 2 in 9 pts and febrile neutropenia (FN) in 2 pts. At 60 mg/m2, two RDs were established: NVB oral 60 mg/m2 weekly/CAP 2000 mg/m2/d D1-D14 q 3w and NVB oral 60 mg/m2 D1, D8/ CAP 2250 mg/m2/d D1-D14 q3w. At 80 mg/m2, the RD was NVB oral 80 mg/m2 D1, D8/CAP 2000 mg/m2/d D1-D14 q 4w. A total of 323 cycles were analyzed. Grade 3 occurred in 14 pts (31.8%) and 6.2% of cycles, grade 4 in 12 pts (27.3%) and 4.3% of cycles. Complications were rare, only 3 episodes of FN. No grade 4 non-haematological toxicity was seen. Grade 3 diarrhea occurred in 2 pts (4.5%) and 0.6% of cycles, no grade 3 HFS, grade 2 HFS occurred in 2 pts (4.5%) and 1.2% of cycles. A total of 18 responses were observed (3 CRs and 15 PRs) yielding a RR of 40.9% [95% CI: 26.3–56.8] in the ITT population. There was no mutual pharmacokinetic interaction when both drugs were co-administered. Conclusion: The combination of NVB oral and CAP is active and can be safely administered in the palliative setting of MBC. The phase II part of the study has started with NVB oral 60 mg/m2/week and CAP 2000 mg/m2/d from D1 to D14 every 3 weeks. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut de Recherche Pierre Fabre, Pierre Fabre