Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.
Department of Oncology, Odense University Hospital, Odense, Denmark.
Cancer Treat Rev. 2014 Jul;40(6):701-15. doi: 10.1016/j.ctrv.2014.02.006. Epub 2014 Feb 28.
Oxaliplatin, irinotecan and 5-fluorouracil in combination with or without targeted therapies are well-documented treatment options for first- and second-line treatments of metastatic colorectal cancer. However, there are much less data on the beneficial effect on systemic therapy in the third-line setting. We therefore performed a systematic review of the current literature on third or later lines of treatment to patients with metastatic colorectal cancer after the use of approved drugs or combinations.
A computer-based literature search was carried out using Pubmed and data reported at international meetings. Original studies reporting ≥15 patients who had previously received 5-fluorouracil, oxaliplatin and irinotecan were included. Furthermore, patients with KRAS wild type tumours should had received EGFR-directed therapy.
Conventional chemotherapeutic agents as capecitabine, mitomycin C, and gemcitabine have limited or no activity. Retreatment with oxaliplatin might be an option in selected patients. In addition, rechallenge with EGFR-directed therapy might be a valuable strategy. Data also suggest that angiogenetic drugs may postpone further progression and prolong survival. Lately, regorafinib has been approved. In conclusion, our current knowledge is based on many retrospective studies, some phase II studies and very few randomized clinical trials. Further prospective phase III trials comparing an investigational drug or combination with best supportive care in third- or later lines of treatment in metastatic colorectal cancer are highly warranted. Identification of predictive biomarkers and improvement of our understanding of molecular mechanisms is crucial.
奥沙利铂、伊立替康和 5-氟尿嘧啶联合或不联合靶向治疗是转移性结直肠癌一线和二线治疗的成熟治疗选择。然而，在三线或更后线治疗中，关于系统治疗的有益效果的数据要少得多。因此，我们对在使用批准的药物或联合治疗后，转移性结直肠癌患者的三线或更后线治疗的当前文献进行了系统评价。
使用 Pubmed 进行了计算机文献检索，并报告了国际会议上的数据。纳入了报告≥15 名先前接受过 5-氟尿嘧啶、奥沙利铂和伊立替康治疗的患者的原始研究。此外，KRAS 野生型肿瘤的患者应接受 EGFR 靶向治疗。
常规化疗药物如卡培他滨、丝裂霉素 C 和吉西他滨的活性有限或没有。在选定的患者中，重新使用奥沙利铂可能是一种选择。此外，重新使用 EGFR 靶向治疗可能是一种有价值的策略。数据还表明，血管生成药物可能会延迟进一步进展并延长生存期。最近，regorafenib 已获得批准。总之，我们目前的知识基于许多回顾性研究、一些 II 期研究和很少的随机临床试验。在转移性结直肠癌的三线或更后线治疗中，进一步进行比较研究药物或联合治疗与最佳支持治疗的前瞻性 III 期试验非常有必要。识别预测生物标志物和提高对分子机制的理解至关重要。
