Phase I-II study of oral vinorelbine (NVBO ) and capecitabine (X) in metastatic breast cancer (MBC): Results of the phase I trial

Abstract

1105 Background: Both NVBO and X are active drugs in MBC. We designed a phase I trial of the combination of these two oral drugs in MBC. Methods: Main inclusion criteria were: documented MBC, ECOG PS 0–1, HER2 negative, and adequate major organ function. Patients could have received chemotherapy (CT) for the disease. Four dose levels were established: 1) NVBO 60 mg/m2, X 1,650 mg/m2/day; 2) NVBO 70 mg/m2, X 1,650 mg/m2/day; 3) NVBO 70 mg/m2, X 2,000 mg/m2/day; 4) NVBO 80 mg/m2, X 2,000 mg/m2/day. No further escalation was attempted. NVBO was given on days 1 and 8 and X was given from day 1 to 14. Cycles were repeated every 3 weeks. Results: Eighteen patients (pts) with MBC entered the study. Median age 61 years (range 44–80), 11 pts (61%) received prior (neo)adjuvant CT. 14 pts (78%) received prior hormone therapy, 13 pts (72%) received no prior chemotherapy for advanced disease and 3 pts (16%) were CT-naïve. After including 3 patients on each dose level no dose limiting toxicity (DLT) was found. No additional dose level was explored due to published experience reporting toxicity when NVBO and X are administered at higher doses. Three additional patients were included on dose levels 3 and 4 without any further DLT. Relative dose intensity of NVBO and X was 84.6% and 83.6% at dose level 3 and 88.8% and 93.6% at dose level 4, respectively. A total of 91 cycles (cy) were analyzed. 13 pts received at least 6 cy as per protocol. Grade 3 neutropenia occurred in 5 pts (28%) and 12% of cy, grade 4 in 1 pt (5%) and 1% of cy. One pt developed febrile neutropenia, not requiring hospitalization. Grade 3 anemia occurred in 1 pt (1 cy). Grade 3–4 nonhematologic toxicities were rare with grade 3 hand-foot syndrome observed in 1 pt (1 cy) and grade 4 constipation (described as nonrelated to treatment) in 1 pt (1 cy). 1 complete response, 4 partial responses and 3 disease stabilization were observed among the 11 evaluable patients for response. Conclusions: The combination of NVBO and X can be safely administered in the palliative setting of MBC and appears to be active. The recommended dose is NVBO 80 mg/m² days 1 and 8 and X 2,000 mg/m²/day days 1 to 14, both drugs administered every 3 weeks. A phase II study with this schedule is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pierre Fabre Iberica