Jahanzeb Mohammad, Mortimer Joanne E, Yunus Furhan, Irwin David H, Speyer James, Koletsky Alan J, Klein Paula, Sabir Tariq, Kronish Lori
The Boca Raton Comprehensive Cancer Center, Florida, USA.
Oncologist. 2002;7(5):410-7. doi: 10.1634/theoncologist.7-5-410.
Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab.
A phase II, open-label trial of intravenous vinorelbine (30 mg/m(2) on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2(+) metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events.
Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3(+) = 82% (18/22) response and IHC 2(+) = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity.
Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2(+) metastatic breast cancer. Further investigation of this novel regimen is planned.
人表皮生长因子受体2（HER2）过表达与侵袭性更强的乳腺癌相关，这类乳腺癌对曲妥珠单抗治疗反应良好。基于曲妥珠单抗的联合方案已显示出比单纯化疗更大的抗肿瘤活性。这些发现，再加上长春瑞滨在乳腺癌中良好的抗肿瘤活性和耐受性，为研究长春瑞滨与曲妥珠单抗的新型联合方案提供了理论依据。
对既往未接受过治疗的HER2阳性转移性乳腺癌患者进行了一项II期开放标签试验，静脉注射长春瑞滨（第1天30mg/m²，之后每周一次）和曲妥珠单抗（第0天4mg/kg，之后每周2mg/kg）。根据3/4级中性粒细胞减少调整长春瑞滨剂量；患者持续接受联合治疗，直至疾病进展或因不良事件而停药。
40例入组患者（中位年龄51岁，范围30 - 82岁）中，37例可评估疗效。总缓解率为78%（29/37，95%置信区间[CI] 62% - 90%），包括4例（11%，95% CI 3% - 25%）完全缓解和25例（68%）部分缓解。客观肿瘤缓解与HER2阳性程度相关：免疫组织化学（IHC）3+ = 82%（18/22）缓解，IHC 2+ = 58%（7/12）缓解。中位疾病进展时间为72周（95% CI 37 - 138周）；中位生存期尚未达到。3/4级中性粒细胞减少是最常见的严重毒性反应，也是剂量降低（9%疗程）和漏用（10%疗程）的原因。无患者发生严重心脏毒性。
对于HER2阳性转移性乳腺癌患者，每周一次长春瑞滨/曲妥珠单抗作为初始治疗具有较高的治疗指数。计划对这一新型方案进行进一步研究。
