晚期结直肠癌分子靶向治疗

摘要/Abstract

摘要：晚期结直肠癌靶向治疗药物主要包括血管内皮生长因子抑制剂和表皮生长因子受体抑制剂。研究表明贝伐珠单抗和西妥昔单抗改善了晚期结直肠癌的预后，但在联合化疗药物方案的选择上稍有差异。西妥昔单抗和贝伐珠单抗改善Kras野生型晚期结直肠癌患者总生存期相似。新的靶向药物阿柏西普、瑞格非尼等的出现，为晚期结直肠癌的靶向治疗提供了更多的选择。

关键词:结直肠肿瘤,分子靶向治疗

Abstract:Targeted agents for advanced colorectal cancer mainly include inhibitors of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Studies show that bevacizumab and cetuximab can improve the prognosis of advanced colorectal cancer patients, but there is slight difference in the choice of chemotherapy regimens when combined with them. Bevacizumab and cetuximab can improve the overall survival of Kras wildtype colorectal cancer patients similarly. The emergence of new targeted drugs such as aflibercept, regorafenib provides more choices for the targeted therapy of advanced colorectal cancer patients.

Key words:Colorectal neoplasms,Molecular targeted therapy

方红艳,周云峰. 晚期结直肠癌分子靶向治疗[J]. 国际肿瘤学杂志, 2016, 43(5): 391-394.

Fang Hongyan, Zhou Yunfeng. Targeted therapy of advanced colorectal cancer[J]. Journal of International Oncology, 2016, 43(5): 391-394.

参考文献

［1］ Desantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014［J］. CA Cancer J Clin, 2014, 64(4): 252-271. DOI: 10.3322/caac.21235. ［2］ Cartwright TH, Yim YM, Yu E, et al. Survival outcomes of bevacizumab beyond progression in metastatic colorectal cancer patients treated in US community oncology［J］. Clin Colorectal Cancer, 2012, 11(4): 238-246. DOI: 10.1016/j.clcc.2012.05.005. ［3］ Bendell JC, BekaiiSaab TS, Cohn AL, et al. Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOXbevacizumab or FOLFIRIbevacizumab: results from Aries, a bevacizumab observational cohort study［J］. Oncologist, 2012, 17(12): 1486-1495. DOI: 10.1634/theoncologist.20120190. ［4］ Cremolini C, Loupakis F, Antoniotti C, et al. Early tumor shrinkage and depth of response predict longterm outcome in metastatic colorectal cancer patients treated with firstline chemotherapy plus bevacizumab: results from phase Ⅲ TRIBE trial by the Gruppo Oncologico del Nord Ovest［J］. Ann Oncol, 2015, 26(6): 1188-1194. DOI: 10.1093/annonc/mdv112. ［5］ Weickhardt AJ, Williams D, Lee C, et al. Vascular endothelial growth factors (VEGF) and VEGF receptor expression as predictive biomarkers for benefit with bevacizumab in metastatic colorectal cancer (mCRC): analysis of the phase Ⅲ MAX study［J］. J Clin Oncol, 2011, 29 (15 Suppl): S3531. ［6］ Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase Ⅲ randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatinbased regimen［J］. J Clin Oncol, 2012, 30(28): 3499-3506. DOI: 10.1200/JCO.2012.42.8201. ［7］ Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebocontrolled, phase 3 trial［J］. Lancet, 2013, 381(9863): 303-312. DOI: 10.1016/S01406736(12)61900X. ［8］ De Roock W, Jonker DJ, Di Nicolantonio F, et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapyrefractory metastatic colorectal cancer treated with cetuximab［J］. JAMA, 2010, 304(16): 1812-1820. DOI: 10.1001/jama.2010.1535. ［9］ Tejpar S, Celik I, Schlichting M, et al. Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with firstline chemotherapy with or without cetuximab［J］. J Clin Oncol, 2012, 30(29): 3570-3577. DOI: 10.1200/JCO.2012.42.2592. ［10］ Pentheroudakis G, Kotoula V, De Roock W, et al. Biomarkers of benefit from cetuximabbased therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes［J］. BMC Cancer, 2013, 13: 49. DOI: 10.1186/147124071349. ［11］ Morelli MP, Overman MJ, Dasari A, et al. Characterizing the patterns of clonal selection in circulating tumor DNA from patients with colorectal cancer refractory to antiEGFR treatment［J］. Ann Oncol, 2015, 26(4): 731-736. DOI: 10.1093/annonc/mdv005. ［12］ Maughan TS, Adams RA, Smith CG, et al. Addition of cetuximab to oxaliplatinbased firstline combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial［J］. Lancet, 2011, 377(9783): 2103-2114. DOI: 10.1016/S01406736(11)606132. ［13］ Tveit KM, Guren T, Glimelius B, et al. Phase Ⅲ trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in firstline treatment of metastatic colorectal cancer: the NORDICVII study［J］. J Clin Oncol, 2012, 30(15): 1755-1762. DOI: 10.1200/JCO.2011.38.0915. ［14］ Peeters M, Price TJ, Cervantes A, et al. Randomized phase Ⅲ study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as secondline treatment in patients with metastatic colorectal cancer［J］. J Clin Oncol, 2010, 28(31): 4706-4713. DOI: 10.1200/JCO.2009.27.6055. ［15］ Douillard JY, Siena S, Cassidy J, et al. Randomized, phase Ⅲ trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as firstline treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study［J］. J Clin Oncol, 2010, 28(31): 4697-4705. DOI: 10.1200/JCO.2009.27.4860. ［16］ Seymour MT, Brown SR, Middleton G, et al. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wildtype, fluorouracilresistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial［J］. Lancet Oncol, 2013, 14(8): 749-759. DOI: 10.1016/S14702045(13)701633. ［17］ Peeters M, Price TJ, Cervantes A, et al. Final results from a randomized phase 3 study of FOLFIRI {+/} panitumumab for secondline treatment of metastatic colorectal cancer［J］. Ann Oncol, 2014, 25(1): 107-116. DOI: 10.1093/annonc/mdt523. ［18］ Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapyrefractory wildtype KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, openlabel, noninferiority phase 3 study［J］. Lancet Oncol, 2014, 15(6): 569-579. DOI: 10.1016/S14702045(14)701184. ［19］ Heinemann V, Von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as firstline treatment for patients with metastatic colorectal cancer (FIRE3): a randomised, openlabel, phase 3 trial［J］. Lancet Oncol, 2014, 15(10): 1065-1075. DOI: 10.1016/S14702045(14)703304. ［20］ Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase Ⅱ study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wildtype KRAS exon 2 metastatic colorectal cancer［J］. J Clin Oncol, 2014, 32(21): 2240-2247. DOI: 10.1200/JCO.2013.53.2473. ［21］ Tol J, Koopman M, Rodenburg CJ, et al. A randomised phase Ⅲ study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in firstline advanced colorectal cancer, the Cairo2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity［J］. Ann Oncol, 2008, 19(4): 734738. DOI: 10.1093/annonc/mdm607. ［22］ Zhang RX, Wu XJ, Wan DS, et al. Celecoxib can prevent capecitabinerelated handfoot syndrome in stage Ⅱ and Ⅲ colorectal cancer patients: result of a singlecenter, prospective randomized phase Ⅲ trial［J］. Ann Oncol, 2012, 23(5): 1348-1353. DOI: 10.1093/annonc/mdr400. ［23］ Le DT, Uram JN, Wang H, et al. PD1 blockade in tumors with mismatchrepair deficiency［J］. N Engl J Med, 2015, 372(26): 2509-2520. DOI: 10.1056/NEJMoa1500596.

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Targeted therapy of advanced colorectal cancer

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