Im Seock-Ah, Kim Sung-Bae, Lee Moon Hee, Im Young-Hyuck, Lee Kyung Hee, Song Hong-Suk, Lee Myung-Ah, Lee Junglim, Lee Nam-Su, Ham Hae Sun, Kim Tae-You, Park Yeon Hee, Lee Kyung Eun, Kim Kee Won, Seo Jae Hong, Lee Soon Nam, Hong Young Seon, Bang Yung-Jue, Kim Woo-Kun, Park Hee-Sook
Breast Cancer Subcommittee, Korean Cancer Study Group, Seoul, Korea.
Oncol Rep. 2005 Aug;14(2):481-7.
The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer (MBC). We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospective assessment of the predictive values of circulating HER2 extracellular domain (ECD) and vascular endothelial growth factor (VEGF). Docetaxel 75 mg/m(2) and epirubicin 75 mg/m(2) were given intravenously every 3 weeks. Prophylactic G-CSF was not used. Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay. Forty MBC patients were enrolled, and 39 patients were evaluable for toxicities and 38 for response. Complete response was observed in 3 (7.9%) patients, partial response in 20 (52.6%) (overall response rate 60.5%), stable disease in 11 (28.9%) and disease progression in 4 (10.5%). After a median follow-up of 22.5 months, the median duration of response was 28 weeks, median time to disease progression was 32 weeks, and median survival was 15.8 months. Two-hundred and fifteen cycles of treatment were administered (median, 6 cycles per patient). Grade 3 and 4 neutropenia were observed during 24 (11.2%) and 74 (35%) cycles respectively, and grade 3 or 4 febrile neutropenia in 24 (11.2%) cycles. Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration (p<0.005) and shorter time to progression (p<0.005). However, elevated VEGF levels were not found to be correlated with response rate or survival. We concluded that the docetaxel and epirubicin combination is an effective first-line treatment in MBC patients and that elevated serum HER2 ECD levels, but not circulating VEGF levels, predict a poor outcome.
蒽环类药物和紫杉烷类药物被认为是转移性乳腺癌（MBC）中最具活性的药物。我们开展了一项多中心II期研究，以评估多西他赛联合表柔比星化疗作为MBC一线治疗的疗效和耐受性，并对循环HER2细胞外结构域（ECD）和血管内皮生长因子（VEGF）的预测价值进行前瞻性评估。多西他赛75mg/m²和表柔比星75mg/m²每3周静脉给药一次。未使用预防性粒细胞集落刺激因子（G-CSF）。采用酶免疫测定法检测治疗前血清HER2 ECD和VEGF水平。纳入40例MBC患者，39例患者可评估毒性，38例可评估疗效。3例（7.9%）患者达到完全缓解，20例（52.6%）患者达到部分缓解（总缓解率60.5%），11例（28.9%）患者疾病稳定，4例（10.5%）患者疾病进展。中位随访22.5个月后，中位缓解持续时间为28周，中位疾病进展时间为32周，中位生存期为15.8个月。共进行了215个周期的治疗（中位，每位患者6个周期）。分别在24个（11.2%）和74个（35%）周期观察到3级和4级中性粒细胞减少，在24个（11.2%）周期观察到3级或4级发热性中性粒细胞减少。发现循环HER2 ECD水平升高与较短的缓解持续时间（p<0.005）和较短的疾病进展时间（p<0.005）相关。然而，未发现VEGF水平升高与缓解率或生存率相关。我们得出结论，多西他赛和表柔比星联合方案是MBC患者有效的一线治疗方案，血清HER2 ECD水平升高而非循环VEGF水平升高预示预后不良。
