Farhat Fadi, Kattan Joseph G, Ghosn Marwan
Department of Hematology-Oncology, Hammoud Hospital University Medical Centre, 652 G. Hammoud Street, Sidon, Lebanon.
Faculty of Medicine, Lebanese University, Beirut, Lebanon.
Cancer Chemother Pharmacol. 2016 May;77(5):1069-77. doi: 10.1007/s00280-016-3027-5. Epub 2016 Apr 8.
Vinorelbine-trastuzumab combination proved to be an effective first-line treatment for patients with locally advanced or metastatic breast cancer (MBC). Oral chemotherapy represents a step forward in MBC management. To improve patients' comfort using the oral form of vinorelbine, we conducted a multicenter phase II study to investigate the efficacy and safety of the oral vinorelbine-trastuzumab combination in women with MBC with human epidermal growth factor receptor 2 (HER2) overexpression.
Main eligibility criteria: HER2-positive disease, no adjuvant chemotherapy within the last 6 months and no prior chemotherapy for MBC. Patients were treated with oral vinorelbine 80 mg/m(2) D1, D8, D15 (following first 3 administrations at 60 mg/m(2) during the first cycle) for a total of 8 cycles (1 cycle = 3 weeks), in combination with trastuzumab 6 mg/kg on D1 (loading dose: 8 mg/kg) every 3 weeks or 4 mg/kg (loading dose: 6 mg/kg) weekly. Response was evaluated every 2 cycles using RECIST 1.0.
objective response rate (ORR); secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
In the full population (n = 26), median age was 50.7 years and median WHO PS 0. Median disease-free interval was 50.7 months [95 % CI (43.6-57.9)]. In the evaluable patients population, ORR was 56 % [95 % CI (34.9-75.6)], including 3 complete responses (12 %) and 11 partial (44 %); 8 (32 %) patients had stable disease resulting in a clinical benefit (or disease control) rate of 88 % [95 % CI (68.8-97.5)]. Median DOR was 7.1 months [95 % CI (3.9-10.2)], median PFS 6.7 months (95 % CI 3.5-10), and median OS 27.9 months (95 % CI 17.4-38.3). Treatment was generally well tolerated with main observed grade 3/4 hematological toxicities being neutropenia (46 %) and anemia (4 %). Grade 3-4 nausea-vomiting were observed in 11.5 % of patients.
Our results confirm the efficacy of oral vinorelbine-trastuzumab combination as a first-line treatment in HER2-positive locally advanced or MBC patients with an acceptable safety profile. Oral vinorelbine-trastuzumab optimizes the convenience of this chemotherapy regimen, especially for patients receiving trastuzumab every 3 weeks.
长春瑞滨-曲妥珠单抗联合治疗被证明是局部晚期或转移性乳腺癌（MBC）患者有效的一线治疗方案。口服化疗是MBC治疗的一大进步。为提高患者使用长春瑞滨口服制剂的舒适度，我们开展了一项多中心II期研究，以调查口服长春瑞滨-曲妥珠单抗联合方案治疗人表皮生长因子受体2（HER2）过表达的MBC女性患者的疗效和安全性。
主要入选标准：HER2阳性疾病，过去6个月内未接受辅助化疗且既往未接受MBC化疗。患者接受口服长春瑞滨80mg/m²，第1、8、15天给药（首周期前3次给药剂量为60mg/m²），共8个周期（1个周期 = 3周），联合曲妥珠单抗，第1天6mg/kg（负荷剂量：8mg/kg），每3周给药一次，或4mg/kg（负荷剂量：6mg/kg），每周给药一次。每2个周期使用RECIST 1.0评估疗效。
客观缓解率（ORR）；次要终点：缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性。
在全部人群（n = 26）中，中位年龄为50.7岁，中位WHO体能状态为0。中位无病间期为50.7个月[95%CI（43.6 - 57.9）]。在可评估患者人群中，ORR为56%[95%CI（34.9 - 75.6）]，包括3例完全缓解（12%）和11例部分缓解（44%）；8例（32%）患者疾病稳定，临床获益（或疾病控制）率为88%[95%CI（68.8 - 97.5）]。中位DOR为7.1个月[95%CI（3.9 - 10.2）]，中位PFS为6.7个月（95%CI 3.5 - 10），中位OS为27.9个月（95%CI 17.4 - 38.3）。治疗总体耐受性良好，主要观察到的3/4级血液学毒性为中性粒细胞减少（46%）和贫血（4%）。11.5%的患者观察到3 - 4级恶心呕吐。
我们的结果证实了口服长春瑞滨-曲妥珠单抗联合方案作为HER2阳性局部晚期或MBC患者一线治疗的疗效，且安全性可接受。口服长春瑞滨-曲妥珠单抗优化了该化疗方案的便利性，尤其对于每3周接受一次曲妥珠单抗治疗的患者。
