Seidman Andrew D, Berry Donald, Cirrincione Constance, Harris Lyndsay, Muss Hyman, Marcom P Kelly, Gipson Grandella, Burstein Harold, Lake Diana, Shapiro Charles L, Ungaro Peter, Norton Larry, Winer Eric, Hudis Clifford
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
J Clin Oncol. 2008 Apr 1;26(10):1642-9. doi: 10.1200/JCO.2007.11.6699.
Phase II trials suggested that weekly paclitaxel might be more effective and less toxic than every-3-weeks administration for metastatic breast cancer (MBC). Cancer and Leukemia Group B (CALGB) protocol 9840 was initiated to address this question. Subsequently trastuzumab was demonstrated to improve outcomes of paclitaxel therapy for human epidermal growth factor receptor-2 (HER-2)-positive patients, and was therefore incorporated. Because inhibition of HER-family signaling had potential efficacy even without HER-2 overexpression, we randomly assigned for trastuzumab in this population.
Patients were randomly assigned to paclitaxel 175 mg/m(2) every 3 weeks or 80 mg/m(2) weekly. After the first 171 patients, all HER-2-positive patients received trastuzumab; HER-2 nonoverexpressors were randomly assigned for trastuzumab, in addition to paclitaxel schedule. A total of 577 patients were treated on 9840. An additional 158 patients were included in analyses, for combined sample of 735. The primary end point was response rate (RR); secondary end points were time to progression (TTP), overall survival, and toxicity. Primary comparisons were between weekly versus every-3-weeks paclitaxel, and trastuzumab versus no trastuzumab in HER-2 nonoverexpressors.
In the combined sample, weekly paclitaxel was superior to every-3-weeks administration: RR (42% v 29%, unadjusted odds ratio [OR] = 1.75; P = .0004), TTP (median, 9 v 5 months; adjusted HR = 1.43; P < .0001), and survival (median, 24 v 12 months; adjusted HR = 1.28; P = .0092). For HER-2 nonoverexpressors, trastuzumab did not improve efficacy. Grade 3 neuropathy was more common with weekly dosing (24% v 12%; P = .0003).
Weekly paclitaxel is more effective than every-3-weeks administration for MBC. Trastuzumab did not improve efficacy for HER-2 nonoverexpressors. Neurotoxicity is a treatment-limiting toxicity for weekly paclitaxel.
II期试验表明，对于转移性乳腺癌（MBC），每周使用紫杉醇可能比每3周给药更有效且毒性更低。癌症与白血病B组（CALGB）启动了9840方案来解决这个问题。随后，曲妥珠单抗被证明可改善人表皮生长因子受体2（HER-2）阳性患者的紫杉醇治疗效果，因此被纳入。由于即使没有HER-2过表达，抑制HER家族信号传导也具有潜在疗效，我们在该人群中对曲妥珠单抗进行了随机分配。
患者被随机分配接受每3周一次的175mg/m²紫杉醇或每周一次的80mg/m²紫杉醇治疗。在前171例患者之后，所有HER-2阳性患者均接受曲妥珠单抗治疗；HER-2非过表达者除了紫杉醇给药方案外，还被随机分配接受曲妥珠单抗治疗。共有577例患者按照9840方案接受治疗。另外158例患者纳入分析，形成735例的合并样本。主要终点为缓解率（RR）；次要终点为疾病进展时间（TTP）、总生存期和毒性。主要比较为每周一次与每3周一次的紫杉醇治疗，以及HER-2非过表达者中曲妥珠单抗与不使用曲妥珠单抗的治疗。
在合并样本中，每周一次的紫杉醇优于每3周一次给药：RR（42%对29%，未调整优势比[OR]=1.75；P=0.0004），TTP（中位数，9个月对5个月；调整后风险比[HR]=1.43；P<0.0001），以及生存期（中位数，24个月对12个月；调整后HR=1.28；P=0.0092）。对于HER-2非过表达者，曲妥珠单抗未改善疗效。3级神经病变在每周给药时更常见（24%对12%；P=0.0003）。
对于MBC，每周一次的紫杉醇比每3周一次给药更有效。曲妥珠单抗未改善HER-2非过表达者的疗效。神经毒性是每周一次紫杉醇治疗的一种限制治疗的毒性。
