Ajani Jaffer A, Moiseyenko Vladimir M, Tjulandin Sergei, Majlis Alejandro, Constenla Manuel, Boni Corrado, Rodrigues Adriano, Fodor Miguel, Chao Yee, Voznyi Edouard, Marabotti Cindy, Van Cutsem Eric
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Clin Oncol. 2007 Aug 1;25(22):3205-9. doi: 10.1200/JCO.2006.10.4968.
For patients with advanced gastric or gastroesophageal cancer (AGGEC) providing clinical benefit with improved palliation is highly desirable. However, a prospective evaluation of clinical benefit in AGGEC patients has never before been reported in a phase III setting.
In a multinational trial (V325), 445 patients were randomly assigned and treated with either docetaxel plus cisplatin and fluorouracil (DCF) or cisplatin and fluorouracil (CF). Clinical benefit was prospectively evaluated in this trial as a secondary end point. The primary measure for clinical benefit analysis was time to definitive worsening by one or more categories of Karnofsky performance status (KPS). Secondary clinical benefit end points included time to 5% definitive weight loss, time to definitive worsening of appetite by one grade, pain-free survival (defined as time to first appearance of pain), and time to first cancer pain-related opioid intake. Clinical benefit assessments were recorded at each clinic visit.
Clinical benefit assessments were performed in more than 75% of patients throughout V325. DCF significantly prolonged time to definitive worsening of KPS compared with CF (median, 6.1 v 4.8 months; hazard ratio, 1.38; 95% CI, 1.08 to 1.76; log-rank P = .009). Although time to definitive weight loss and time to definitive worsening of appetite favored DCF, the results were not statistically significant. Pain-free survival and time to first cancer pain-related opioid intake were comparable.
To our knowledge, V325 is the first phase III trial to report clinical benefit in AGGEC patients. Clinical benefit was assessed beyond protocol-specific chemotherapy. The addition of D to CF not only significantly improved clinical benefit but also improved quality of life, time to progression, and overall survival compared with CF.
对于晚期胃癌或胃食管癌（AGGEC）患者而言，能带来临床获益并改善姑息治疗效果是非常理想的。然而，此前从未有过在III期研究中对AGGEC患者的临床获益进行前瞻性评估的报道。
在一项跨国试验（V325）中，445例患者被随机分组，分别接受多西他赛联合顺铂和氟尿嘧啶（DCF）或顺铂和氟尿嘧啶（CF）治疗。在该试验中，临床获益作为次要终点进行前瞻性评估。临床获益分析的主要指标是卡诺夫斯基功能状态（KPS）一项或多项指标明确恶化的时间。次要临床获益终点包括体重明确下降5%的时间、食欲明确恶化一级的时间、无疼痛生存期（定义为首次出现疼痛的时间）以及首次因癌症疼痛而使用阿片类药物的时间。每次门诊就诊时记录临床获益评估情况。
在整个V325试验中，超过75%的患者进行了临床获益评估。与CF相比，DCF显著延长了KPS明确恶化的时间（中位数，6.1对4.8个月；风险比，1.38；95%CI，1.08至1.76；对数秩检验P = 0.009）。虽然体重明确下降的时间和食欲明确恶化的时间有利于DCF，但结果无统计学意义。无疼痛生存期和首次因癌症疼痛而使用阿片类药物的时间相当。
据我们所知，V325是首个报道AGGEC患者临床获益的III期试验。临床获益评估超出了方案规定的化疗范围。与CF相比，CF方案中加入D不仅显著改善了临床获益，还改善了生活质量、疾病进展时间和总生存期。
