大肠癌的分子靶向治疗

摘要/Abstract

摘要： 大肠癌是最常见的恶性肿瘤之一,晚期大肠癌的治疗主要依靠氟尿嘧啶类、草酸铂和伊立替康等药物为主的化疗,但易产生耐药性。近年来靶向治疗的成功应用提高了晚期大肠癌患者的生存率。本文就目前大肠癌的靶向治疗方面进行综述。

关键词: 大肠癌, 靶向治疗, 贝伐珠单克隆抗体, 西妥昔单克隆抗体, 帕尼单克隆抗体

Abstract: Colorectal cancer is one of the most common malignant tumors. For patients with metastatic colorectal cancer (mCRC), chemotherapy with fluoropyrimidines, oxaliplatin and irinotecan is the main treatment, but multi-drug resistance occurs very often. In recent years the successful development of targeted therapy improves survival in patients with mCRC. This article reviews the development of targeted agents for the treatment of mCRC.

Key words: Colorectal cancer, Targeted therapy, Bevacizumab, Cetuximab, Panitumumab

中图分类号:

R735

盛莉莉, 吉兆宁. 大肠癌的分子靶向治疗[J]. 中国临床药理学与治疗学, 2013, 18(6): 715-720.

SHENG Li-li, JI Zhao-ning. Molecular targeted therapy of colorectal cancer[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(6): 715-720.

参考文献

[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 69-90.
[2] Takahashi Y, Tucker SL, Kitadai Y, et al. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer[J]. Arch Surg, 1997, 132(5): 541-546.
[3] Fan F, Wey JS, Mccarty MF, et al. Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells [J]. Oncogene, 2005, 24(16): 2647-2653.
[4] Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer[J]. J Clin Oncol, 2001, 19(3): 843-850.
[5] Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer[J]. N Engl J Med, 2004, 350(23): 2335-2342.
[6] Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study[J]. J Clin Oncol, 2008, 26(12): 2013-2019.
[7] Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200[J]. J Clin Oncol, 2007, 25(12): 1539-1544.
[8] Horita Y, Yamada Y, Kato K, et al. Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial [J]. Int J Clin Oncol, 2012, 17(6): 604-609.
[9] Dirk A, Thierry A, Jaafar B, et al. Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: Results of a randomized phase III intergroup study (TML study)[J]. J Clin Oncol, 2012, 30(suppl): A3503.
[10]Allegra CJ, Yothers G, O'Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08[J]. J Clin Oncol, 2011, 29(1): 11-16.
[11]Gramont AD, Cutsem EV, Tabernero J, et al. AVANT:Results from a randomized,three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer[J]. J Clin Oncol, 2011, 29(suppl): 362.
[12] Fransen K, Klintenas M, Osterstrom A, et al. Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas [J]. Carcinogenesis, 2004, 25(4): 527-533.
[13]Roberts RB, Min L, Washington MK, et al. Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis [J]. Proc Natl Acad Sci U S A, 2002, 99(3): 1521-1526.
[14]Sobrero AF, Maurel J, Fehrenbacher L, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer[J]. J Clin Oncol, 2008, 26(14): 2311-2319.
[15] Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer [J]. N Engl J Med, 2009, 360(14): 1408-1417.
[16]Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer [J]. J Clin Oncol, 2009, 27(5): 663-671.
[17]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.
[18]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.
[19]Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer [J]. J Clin Oncol, 2007, 25(13): 1658-1664.
[20]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.
[21]Peeters M, Price T J, 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.
[22]Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer [J]. N Engl J Med, 2009, 360(6): 563-572.
[23]Hecht JR, Mitchell E, Chidiac T, et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer [J]. J Clin Oncol, 2009, 27(5): 672-680.
[24]Poindessous V, Ouaret D, El OK, et al. EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies [J]. Clin Cancer Res, 2011, 17(20): 6522-6530.
[25]Christophe T, Benoit S, Werner S, et al. Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy and safety results of the International GERCOR DREAM phase III trial[J]. J Clin Oncol, 2012, 30 (suppl): LBA3500.
[26]Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects[J]. Proc Natl Acad Sci U S A, 2002, 99(17): 11393-11398.
[27]Kim ES, Serur A, Huang J, et al. Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma[J]. Proc Natl Acad Sci U S A, 2002, 99(17): 11399-11404.
[28]Carmen J, Radek L, Josep T, et al. Effects of prior bevacizumab (B) use on outcomes from the VELOUR study: A phase III study of aflibercept (Afl) and FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin regimen [J]. J Clin Oncol, 2012, 30(suppl): 3505.
[29]Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity[J]. Int J Cancer, 2011, 129(1): 245-255.
[30]Eric V, Alberto F, Salvatore S, et al. Phase III CORRECT trial of regorafenib in metastatic colorectal cancer (mCRC) [J]. J Clin Oncol, 2012, 30(suppl): 3505.