Sledge George W
Indiana University, School of Medicine, Indianapolis, Indiana, USA.
Oncology (Williston Park). 2003 Dec;17(12 Suppl 14):33-5.
Gemcitabine (Gemzar) and paclitaxel show good activity as single agents and combined in metastatic breast cancer, and the combination of paclitaxel/trastuzumab (Herceptin) has been shown to prolong time to disease progression and survival significantly in this setting. Preclinical data indicate additive or synergistic effects of gemcitabine and trastuzumab in HER2-positive human breast cancer cell lines. In a phase II trial, patients with HER2-overexpressing metastatic breast cancer who had received no prior chemotherapy for metastatic disease received gemcitabine at 1,200 mg/m2 on days 1 and 8 and paclitaxel at 175 mg/m2 on day 1 every 21 days for six cycles plus trastuzumab at an initial loading dose of 4 mg/kg followed by 2 mg/kg weekly; patients without progressive disease after six cycles continued to receive trastuzumab until disease progression. Overall, objective response was observed in 28 (67%) of 42 evaluable patients, including complete response in 4 (10%) and partial response in 24 (57%); stable disease was observed in 7 (17%) and progressive disease was observed in 6 (14%). Median time to treatment failure was 9+ months. Median overall survival has not yet been reached, but is estimated at approximately 27 months. Significant toxicities apart from neutropenia were uncommon. The triplet combination of gemcitabine, paclitaxel, and trastuzumab is highly active and well tolerated in patients with HER2-overexpressing metastatic breast cancer.
吉西他滨（健择）和紫杉醇单药治疗转移性乳腺癌时显示出良好活性，二者联合使用也有良好效果，并且在这种情况下，紫杉醇/曲妥珠单抗（赫赛汀）联合使用已被证明能显著延长疾病进展时间和生存期。临床前数据表明，吉西他滨和曲妥珠单抗在HER2阳性的人乳腺癌细胞系中具有相加或协同作用。在一项II期试验中，既往未接受过转移性疾病化疗的HER2过表达转移性乳腺癌患者，每21天为一个周期，在第1天和第8天接受1200mg/m²的吉西他滨，第1天接受175mg/m²的紫杉醇，共六个周期，同时初始负荷剂量为4mg/kg的曲妥珠单抗，随后每周2mg/kg；六个周期后无疾病进展的患者继续接受曲妥珠单抗治疗直至疾病进展。总体而言，42例可评估患者中有28例（67%）观察到客观缓解，包括4例（10%）完全缓解和24例（57%）部分缓解；7例（17%）疾病稳定，6例（14%）疾病进展。治疗失败的中位时间为9个多月。总生存期的中位数尚未达到，但估计约为27个月。除中性粒细胞减少外，显著的毒性反应并不常见。吉西他滨、紫杉醇和曲妥珠单抗三联组合对HER2过表达转移性乳腺癌患者具有高活性且耐受性良好。
