A Phase II Study of Capecitabine, Oxaliplatin, and Bevacizumab in the Treatment of Metastatic Esophagogastric Adenocarcinomas. (13th March 2013) - Uronis, Hope E.
Abstract : Background: Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. We evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. Methods: Thirty‐seven patients with metastatic or unresectable gastric/gastroesophageal junction tumors were enrolled and treated with capecitabine 850 mg/m 2 BID on days 1–14, and oxaliplatin 130 mg/m 2 with bevacizumab 15 mg/kg on day 1 of a 21‐day cycle. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Neuropilin‐1 (NRP1) and ‐2 (NRP2) mRNA expression was evaluated in archived tumor. Results: Thirty‐five patients were evaluable for efficacy. Median PFS was 7.2 months; median OS was 10.8 months. RR was estimated at 51.4%. The regimen was tolerable with expected drug class‐related toxicities. NRP2 mRNA levels significantly correlated with PFS ( p = 0.042) and showed a trend toward significance with OS ( p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome. Conclusions: Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumab‐containing regimens in metastatic gastroesophageal cancer. Abstract : 摘要 背景 ：食管癌和胃癌通常发现时已处于晚期。全身化疗是其主要的治疗方法，但当前方案的生存率仍然较低。本研究对卡培他滨、奥沙利铂和贝伐珠单抗联合用药在转移性食管胃腺癌治疗中的安全性、耐受性和有效性进行了评估。 方法： 37例转移性或不能切除的胃/胃食管连接部肿瘤患者入组并接受治疗。21天为一个化疗周期。第1∼ 14天给予卡培他滨850mg/m 2 ，每日2次；第1天给予奥沙利铂130mg/m 2 和贝伐珠单抗15mg/kg。主要终点指标是无进展生存（PFS）。次要终点指标包括缓解率（RR）和总生存（OS）。并对留存肿瘤组织中的神经纤毛蛋白1（NRP1）和2（NRP2）mRNA的表达情况进行了评估。 结果： 35例患者可评价有效性。中位PFS为7.2个月，中位OS为10.8个月，估计RR为51.4%。本方案可以耐受，伴可预期的药物级别相关毒性。NRP2 mRNA的水平与PFS相关，有统计学意义（ p =0.042），且与OS的相关性呈现显著性的趋势（ p =0.051）。NRP1表达水平越高转归越差的趋势未获得统计学意义。 结论： 贝伐珠单抗可以安全地用于转移性食管胃腺癌患者的化疗。对于转移性胃食管癌，联合应用卡培他滨、奥沙利铂加贝伐珠单抗的有效性与其他包含贝伐珠单抗的方案相近。