1. Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.
2. Professor, Chairman of the department of Hematology and Medical Oncology at Saint-Joseph University Faculty of Medicine, Beirut, Lebanon.
J Cancer. 2014 Mar 29;5(5):351-9. doi: 10.7150/jca.8304. eCollection 2014.
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.
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.
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%).
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.
许多二期临床试验研究了吉西他滨（G）和长春瑞滨（V）联合用于治疗多西紫杉醇和蒽环类药物预处理的转移性乳腺癌（MBC），但结果不一。本研究旨在探讨该联合方案在多西紫杉醇和蒽环类药物预处理的 MBC 患者中的有效性和耐受性。
首先进行了 I 期研究，以确定 MBC 患者中 G 和 V 联合的最大耐受剂量（MTD）。然后，II 期研究评估了该联合方案在 MTD 下的反应率、中位无进展生存期（TTP）、总生存期（OS）以及毒性。
9 名患者入组 I 期研究。G 的 MTD 确定为 700mg/m2，于第 1 天和第 8 天给药，V 的 MTD 确定为 15mg/m2，于第 2 天和第 9 天给药，每 21 天给药一次。25 名患者中有 21 名可评估疗效。无完全或部分缓解，6 名患者（24.0%）疾病稳定，15 名患者（60.0%）疾病进展。中位 TTP 为 2 个月，中位 OS 为 10 个月。3/4 级中性粒细胞减少是主要血液学毒性，发生于 52%的周期。最常见的 3/4 级非血液学毒性为疲劳（18%）、肌痛（17%）和关节痛（13%）。
在多西紫杉醇和蒽环类药物预处理的 MBC 患者中，该联合方案并未诱导部分或完全缓解，因此无效。未来的研究应评估其他化疗药物或联合方案。
