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

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Author(s): A. Kalykaki,
S. Agelaki, A. Kotsakis, L. Vamvakas, V. Bozionelou, K. Kalbakis, N.
Androulakis, V. Georgoulias, D. Mavroudis; Department of Medical
Oncology, University Hospital, Heraklion, Greece
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.
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.