Lam Ka On, Lee Victor Ho Fun, Liu Rico Kin Yin, Leung To Wai, Kwong Dora Lai Wan
Department of Clinical Oncology, Faculty of Medicine, The University of Hong Kong; ; Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, SAR, P.R. China.
Oncol Lett. 2013 Feb;5(2):637-640. doi: 10.3892/ol.2012.1045. Epub 2012 Nov 26.
Bevacizumab and cetuximab both improve treatment efficacy when administered with chemotherapy for metastatic colorectal carcinoma (mCRC). Cetuximab has enhanced efficacy in Kras wild-type tumors. However, inferior outcomes have been demonstrated concerning the concurrent use of bevacizumab and cetuximab with chemotherapy. There is an urgent need to define the optimal sequence of use of these two agents. With regard to the pre-clinical data that increased VEGF expression is associated with acquired resistance to anti-EGFR antibody, we performed a retrospective analysis on the outcomes of patients who received bevacizumab-containing regimens after cetuximab failure in Kras wild-type mCRC. From January 2006 to December 2011, patients who received bevacizumab-containing regimens for mCRC in our institution were reviewed. Patients were eligible for further analysis if the following criteria were met: i) Kras wild-type mCRC; ii) chemotherapy and cetuximab received as immediate prior treatment; iii) chemotherapy and bevacizumab received as the index line of treatment; and iv) imaging conducted for response evaluation. Outcome measures included median progression-free survival (mPFS) and objective response rate (ORR). Targeted adverse events were recorded in accordance with two prospective observational cohort studies; the BRiTE and BEAT studies. Fifty patients who received bevacizumab-containing regimens were reviewed and 18 of them met the criteria for further analysis. After a median follow-up of 12.1 months, the mPFS for the total group of patients was 26.3 weeks (95% CI, 19.5-33.0 weeks) with an ORR of 38.9%. Two patients (11.1%) had hypertension that required additional anti-hypertensive drugs and one patient did not survive due to a bowel perforation. No arterial thromboembolic events (ATEs), post-operative wound-healing complications (POWHCs) or grade III/IV bleeding were observed. In patients with Kras wild-type mCRC, bevacizumab-containing regimens following cetuximab failure have modest activity and manageable toxicity.
贝伐单抗和西妥昔单抗与化疗联合应用于转移性结直肠癌（mCRC）时均能提高治疗效果。西妥昔单抗在Kras野生型肿瘤中疗效增强。然而，贝伐单抗和西妥昔单抗与化疗同时使用的疗效较差。迫切需要确定这两种药物的最佳使用顺序。关于临床前数据表明VEGF表达增加与抗EGFR抗体获得性耐药相关，我们对Kras野生型mCRC患者在西妥昔单抗治疗失败后接受含贝伐单抗方案治疗的结局进行了回顾性分析。2006年1月至2011年12月，对我院接受含贝伐单抗方案治疗mCRC的患者进行了回顾。如果符合以下标准，患者有资格进行进一步分析：i）Kras野生型mCRC；ii）之前立即接受过化疗和西妥昔单抗治疗；iii）化疗和贝伐单抗作为索引治疗线；iv）进行影像学检查以评估反应。结局指标包括中位无进展生存期（mPFS）和客观缓解率（ORR）。根据两项前瞻性观察队列研究（BRiTE和BEAT研究）记录靶向不良事件。对50例接受含贝伐单抗方案治疗的患者进行了回顾，其中18例符合进一步分析标准。中位随访12.1个月后，患者总体组的mPFS为26.3周（95%CI，19.5 - 33.0周），ORR为38.9%。2例患者（11.1%）出现高血压，需要额外的抗高血压药物治疗，1例患者因肠穿孔死亡。未观察到动脉血栓栓塞事件（ATEs）、术后伤口愈合并发症（POWHCs）或III/IV级出血。在Kras野生型mCRC患者中，西妥昔单抗治疗失败后含贝伐单抗方案具有适度的活性和可管理的毒性。
