Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Cancer. 2011 May 15;117(10):2050-7. doi: 10.1002/cncr.25729. Epub 2010 Nov 29.
The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes.
Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m(2) on days 1 and 8) plus S-1 (35 mg/m(2) each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m(2) each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis.
Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥ 3 toxicity was neutropenia. Grade ≥ 3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis.
The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer.
本研究旨在比较两种每周一次的多西紫杉醇为基础的方案作为晚期胃癌的一线治疗，并探讨富含半胱氨酸的酸性分泌蛋白（SPARC）的表达及其预测治疗相关临床结局的能力。
患者被随机选择接受 3 个每周周期的多西紫杉醇（35mg/m2，第 1 和第 8 天）加 S-1（35mg/m2，每天两次，第 1-14 天）（DS）或多西紫杉醇加顺铂（35mg/m2，第 1 和第 8 天）（DC）。终点包括总缓解率（主要终点）、生存、毒性和生活质量（次要终点）。通过免疫组织化学分析评估原发性胃肿瘤化疗前标本中 SPARC 的表达。
共纳入 80 例患者。DS 组的确认总缓解率为 46%（95%置信区间，30%-62%），DC 组为 24%（95%置信区间，11%-38%）。DS 和 DC 的中位无进展生存期分别为 7.3 和 4.9 个月，总生存期分别为 16.0 和 8.3 个月。最常见的≥3 级毒性为中性粒细胞减少症。DS 组最常见的≥3 级粘膜炎（18%）和手足综合征（8%），而 DC 组更常见的是厌食（20%）和乏力（20%）。多变量分析显示，SPARC 高表达与多西紫杉醇化疗时的早期进展（危险比，3.67；P =.042）和总体生存不良（危险比，2.01；P =.010）相关。
本研究结果表明 DS 方案优于 DC 方案，适合进一步进行 3 期研究。研究结果表明，每周一次的多西紫杉醇分剂量可减轻血液学毒性而不影响疗效，而 SPARC 表达可能有助于晚期胃癌的个体化治疗。
