Dotan Efrat, Meropol Neal J, Burtness Barbara, Denlinger Crystal S, Lee James, Mintzer David, Zhu Fang, Ruth Karen, Tuttle Holly, Sylvester Judi, Cohen Steven J
Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
J Gastrointest Cancer. 2012 Dec;43(4):562-9. doi: 10.1007/s12029-012-9368-3.
Dual inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) demonstrated initial promise in clinical trials. This phase II study tested the efficacy and safety of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as first-line treatment for metastatic colorectal cancer patients.
Patients were randomized to receive capecitabine 850 mg/m2 PO twice daily for 14 days, oxaliplatin 130 mg/ m2 IV day 1, and cetuximab 400 mg/m2 IV loading dose followed by 250 mg/m2 IV days 1, 8, and 15 with (arm A) or without (Arm B) bevacizumab 7.5 mg/kg IV day 1 every 21 days. Tumor samples were collected and retrospectively analyzed for KRAS mutation status. The primary endpoint was response rate, with time to progression (TTP) and overall survival (OS) as secondary objectives.
Twenty-three patients (12 in arm A, 11 in arm B) were enrolled onto the study. Median follow-up was 25.9 months. Both treatments were well tolerated, with expected higher rates of grade 1/2 hypertension and bleeding in arm A. The overall response rate was 54% (36.4% in arm A and 72.7% in arm B). Median time to progression was 8.7 months in arm A and 14.4 months in arm B. The median survival was 18.0 months in arm A and 42.5 months in arm B. The study was prematurely terminated after other studies reported inferior outcomes with dual antibody therapy.
Although terminated early, the study supports the detrimental effect of combining VEGF and EGFR inhibition in metastatic colorectal cancer.
血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）的双重抑制在临床试验中显示出初步前景。这项II期研究测试了卡培他滨、奥沙利铂和西妥昔单抗联合或不联合贝伐单抗作为转移性结直肠癌患者一线治疗的疗效和安全性。
患者被随机分配接受卡培他滨850mg/m²口服，每日两次，共14天；奥沙利铂130mg/m²静脉滴注，第1天；西妥昔单抗400mg/m²静脉滴注负荷剂量，随后第1、8和15天给予250mg/m²静脉滴注，A组联合贝伐单抗7.5mg/kg静脉滴注，第1天，每21天一次，B组不联合。收集肿瘤样本并回顾性分析KRAS突变状态。主要终点是缓解率，次要目标是疾病进展时间（TTP）和总生存期（OS）。
23例患者（A组12例，B组11例）入组本研究。中位随访时间为25.9个月。两种治疗耐受性良好，A组1/2级高血压和出血发生率预期较高。总缓解率为54%（A组为36.4%，B组为72.7%）。A组疾病进展中位时间为8.7个月，B组为14.4个月。A组中位生存期为18.0个月，B组为42.5个月。在其他研究报告双抗体治疗效果较差后，本研究提前终止。
尽管研究提前终止，但该研究支持在转移性结直肠癌中联合抑制VEGF和EGFR具有有害作用。
