Limentani Steven A, Brufsky Adam M, Erban John K, Jahanzeb Mohammed, Lewis Deborah
Carolinas Hematology-Oncology Associates, The Blumenthal Cancer Center, University of North Carolina, Charlotte, NC 28203, USA.
J Clin Oncol. 2007 Apr 1;25(10):1232-8. doi: 10.1200/JCO.2005.05.3306. Epub 2007 Feb 12.
To evaluate the combination of docetaxel, vinorelbine, and trastuzumab as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)--overexpressing breast cancer.
Patients with stage IIB or III breast cancer, including inflammatory disease, and HER2 overexpression (determined by fluorescent in situ hybridization) were treated with six cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 administered every 14 days with granulocyte colony-stimulating factor and quinolone prophylaxis. Trastuzumab was administered as a 4 mg/kg loading dose followed by 2 mg/kg weekly for 12 weeks. The primary efficacy end point was pathologic complete response (pCR) in the breast.
Of 31 enrolled patients, 68% had T3 or T4 tumors and 90% were clinically node positive. Twelve patients (39%; 95% CI, 21.6% to 55.9%) achieved pCR in the breast and lymph nodes and 14 patients (45%; 95% CI, 27.6% to 62.7%) achieved pCR in the breast alone, and 19 patients (61%; 95% CI, 44.1% to 78.4%) were node negative after neoadjuvant therapy. Clinical response was documented in 29 patients (94%; 95% CI, 78.6% to 99.2%) with 26 complete responses (84%; 95% CI, 70.9% to 96.8%). The most commonly reported grade 3/4 toxicities were neutropenia (97%), febrile neutropenia (22%), anemia (6%), mucositis/stomatitis (6%), constipation (6%), and skin rash (6%).
With clinical response and pCR rates of 94% and 39%, respectively, docetaxel, vinorelbine, and trastuzumab is a highly active neoadjuvant therapy for HER2-overexpressing locally advanced breast cancer. Although well tolerated overall, significant febrile neutropenia was observed despite prophylactic measures; therefore, evaluating a similar regimen using lower docetaxel and/or vinorelbine doses is warranted.
评估多西他赛、长春瑞滨和曲妥珠单抗联合作为人表皮生长因子受体2（HER2）过表达乳腺癌新辅助治疗的效果。
IIB期或III期乳腺癌患者，包括炎性疾病患者，且HER2过表达（通过荧光原位杂交确定），接受六个周期的多西他赛60mg/m²和长春瑞滨45mg/m²治疗，每14天给药一次，并给予粒细胞集落刺激因子和喹诺酮预防。曲妥珠单抗以4mg/kg的负荷剂量给药，随后每周2mg/kg，共12周。主要疗效终点为乳腺病理完全缓解（pCR）。
31例入组患者中，68%有T3或T4肿瘤，90%临床淋巴结阳性。12例患者（39%；95%CI，21.6%至55.9%）乳腺和淋巴结达到pCR，14例患者（45%；95%CI，27.6%至62.7%）仅乳腺达到pCR，19例患者（61%；95%CI，44.1%至78.4%）新辅助治疗后淋巴结阴性。29例患者（94%；95%CI，78.6%至99.2%）记录有临床反应，其中26例完全缓解（84%；95%CI，70.9%至96.8%）。最常报告的3/4级毒性为中性粒细胞减少（97%）、发热性中性粒细胞减少（22%）、贫血（6%）、粘膜炎/口腔炎（6%）、便秘（6%）和皮疹（6%）。
多西他赛、长春瑞滨和曲妥珠单抗作为HER2过表达局部晚期乳腺癌的新辅助治疗，临床反应率和pCR率分别为94%和39%，是一种高活性的治疗方法。尽管总体耐受性良好，但尽管采取了预防措施仍观察到显著的发热性中性粒细胞减少；因此，有必要评估使用较低剂量多西他赛和/或长春瑞滨的类似方案。
