A phase I study of oral metronomic vinorelbine plus capecitabine in patients with metastatic breast cancer

1127 Background: The combination of capecitabine plus intravenous vinorelbine has shown substantial activity in anthracycline and/or taxane pretreated patients with metastatic breast cancer (MBC). The metronomic administration may be associated with reduced toxicity and enhanced efficacy. We conducted a phase I study to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of capecitabine plus oral vinorelbine administered metronomically in patients with MBC. Methods: Patients were treated with vinorelbine (30–60 mg total dose) p.o three times per week continuously and capecitabine (800–1250 mg/m2 twice a day) from day 1 to 14 in three week cycles. DLT was defined during the first cycle as grade (G) 4 neutropenia or thrombocytopenia, febrile neutropenia, any ≥ G 3 non-hematological toxicity, and any delay of treatment due to toxicity. Results: To date 27 patients have been enrolled on 7 different dose levels. Treatment was first line for 16 and second line for 11 patients. DLTs included G3 febrile neutropenia and treatment delay due to G2 neutropenia occurring in 1 patient each, at dose level 4 and G3 diarrhea and treatment delay due to G2 neutropenia in 1 patient each, at dose level 7. The MTD has not yet been reached. Hematologic and nonhematological toxicities were generally mild to moderate. Most common were myelosuppression, asthenia, nausea, and diarrhea. Nine objective responses were observed with 2 complete and 7 partial. Conclusions: Vinorelbine 60 mg three times a week in combination with capecitabine 1250mg/m2 twice a day, has been well tolerated. Enrollment is ongoing. Updated data will be presented at the meeting. No significant financial relationships to disclose.