Shah Manish A, Ramanathan Ramesh K, Ilson David H, Levnor Alissa, D'Adamo David, O'Reilly Eileen, Tse Archie, Trocola Robin, Schwartz Lawrence, Capanu Marinela, Schwartz Gary K, Kelsen David P
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
J Clin Oncol. 2006 Nov 20;24(33):5201-6. doi: 10.1200/JCO.2006.08.0887.
Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival.
Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed.
Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.
贝伐单抗与化疗联合应用可提高多种实体瘤恶性肿瘤的生存率。我们评估了在胃癌和胃食管交界（GEJ）腺癌治疗中，添加贝伐单抗至化疗方案的疗效和安全性。
47例转移性或不可切除的胃/GEJ腺癌患者，在第1天接受15mg/kg贝伐单抗治疗，在第1天和第8天接受65mg/m²伊立替康及30mg/m²顺铂治疗，每21天为一个周期。主要终点是证明疾病进展时间比历史值提高50%。次要终点包括安全性、缓解率和生存率。
患者特征如下：中位年龄59岁（范围25至75岁）；卡诺夫斯基体能状态90%（70%至100%）；男女比例为34:13；胃癌/GEJ癌比例为24:23。中位随访时间为12.2个月，中位疾病进展时间为8.3个月（95%CI，5.5至9.9个月）。在34例可测量疾病的患者中，总缓解率为65%（95%CI，46%至80%）。中位生存期为12.3个月（95%CI，11.3至17.2个月）。我们未观察到化疗相关毒性增加。可能与贝伐单抗相关的毒性包括3级高血压发生率为28%，2例胃穿孔患者和1例接近穿孔患者（6%），以及1例心肌梗死患者（2%）。25%的患者发生3至4级血栓栓塞事件。尽管40例患者的原发肿瘤未切除，但我们仅观察到1例严重上消化道出血患者。
即使存在原发性胃癌和GEJ肿瘤，贝伐单抗也可与化疗安全联用。缓解率、疾病进展时间（TTP）和总生存期令人鼓舞，TTP比历史对照提高了75%。贝伐单抗在胃癌和GEJ癌中的进一步研发是有必要的。
