Phase I and II Study of Gemcitabine and Vinorelbine in Heavily Pretreated Patients with Metastatic Breast Cancer and Review of the Literature.

Background: Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the treatment of metastatic breast cancer (MBC) with variable outcomes. This study was conducted to explore whether this combination was effective and tolerable in MBC patients who were heavily pretreated with anthracyclines and taxanes. Methods: A phase I study was conducted first to establish the maximum tolerated dose (MTD) of the G and V combination in MBC patients. Then, a phase II study evaluated the response rates, the median time to progression (TTP), the overall survival (OS) as well as the toxicities resulting from this combination at the MTD. Results: Nine patients were enrolled in the phase I study. The MTD was identified as 700mg/m(2) of G on days 1 and 8 in combination with 15 mg/m(2) of V on days 2 and 9, every 21 days. Twenty-one of 25 patients involved in the phase II study were evaluable for response. No complete or partial responses were achieved; 6 patients (24.0%) had stable disease and 15 (60.0%) progressed. The median TTP was 2 months and the median OS 10 months. Grade 3/4 Neutropenia was the major hematologic toxicity, occurring in 52% of the cycles. The most common non-hematologic grade 3/4 toxicities were fatigue (18%), myalgias (17%) and arthralgias (13%). Conclusion: In heavily pretreated patients with MBC, the combination of G and V at the doses stated above was ineffective as it did not induce partial or complete responses. Other chemotherapy agents or combinations should be evaluated in future studies.