(Chin J New Drugs Clin Rem),2015 9, )

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1 692 [ ] (2015) [DOI ] /j.cnki.xyylc Ziv- 宋 敏 (, ) [ ] Ziv- ; ;, [ ] (mcrc) 2012 Ziv- mcrc, Ziv-, (VEGF), Ziv- mcrc, Ziv- mcrc [ ] R979.1 [ ] A Progression of Ziv- aflibercept on metastatic colorectal cancer SONG Min (Department of Pharmacy, Xiamen University Affiliated Zhongshan Hospital, Xiamen FUJIAN , China) [KEY WORDS] Ziv- aflibercept; colorectal neoplasms; receptors, vascular endothelial growth factor [ ABSTRACT] Targeted drug therapy for specific molecular targets has become a new direction of treatment for metastatic colorectal cancer (mcrc). Ziv- Aflibercept was approved by the U.S. Food and Drug Administration for use in the patients with mcrc in Ziv - Aflibercept is a novel recombinant fusion protein which can inhibit growth and metastasis of tumor by blocking vascular endothelial growth factor ( VEGF) receptors. A phase clinical trial showed the benefit of Ziv - aflibercept on the overall survival of mcrc patients. In this paper, the progression of Ziv- aflibercept on mcrc are summarized. (colorectal cancer, CRC) (oxaliplatin), (irinotecan) (fluorouracil), CRC 120,, 60 [1] CRC 40 ( 30.7/10 ), CRC, 58, 12 ~ 18 [2],, 25% CRC,, [3] CRC CRC mcrc, 5 12% [4] (overall survival, OS), 6 (mcrc), 24 ~ 28 [5] [ ] [ ] [ ],,,,, songmin_csu@hotmail.com

2 693 ( cetuximab) Ziv- (1.7 ~ 5.1 d) (panitumumab) (regorafenib) (0.3 ~ 7.0 mg kg -1, iv), (bevacizumab) Ziv- (Ziv-aflibercept, AVE0005, Zaltrap), [8] (epithelial growth factor receptor, EGFR) [6], KRAS mcrc, 0.3 mg kg -1 (, (VEGFR1 VEGFR2 VEGFR3 TIE- 2), (c- kit RET RAF- 1 BRAF) (PDGFR FGFR) 4 mg L mg L -1 Ziv- [7], (vascular mg kg -1, endothelial growth factor, VEGF) Ziv- Ziv- 4.0 mg kg -1, ,, Ziv- (FDA) Ziv- FOLFIRI ( ): VEGF- A VEGF- (, ), VEGF [8] mcrc, Ziv- [10-12] Ziv- mcrc, (maximumtolerated dose, MTD), VEGF 6 B VEGF- C VEGF- D VEGF- E 2010 LOCKHART [10] Ziv- (PIGF), VEGF, Ziv- 47, 7 mcrc VEGF,,, 2, 7, VEGF- A, VEGF- B PIGF, [8, 9] Ziv-, 13 Ziv- MTD ( ~ 6 2 Ziv- [8] a/pmol L -1 /d Ziv- VEGF- A VEGF- B PIGF ~ 6 VEGF- A a,, 2.0 ~ 7.0 mg kg -1, [8, 10], Ziv- 0.3 mg kg -1 1/10) 7.0 mg kg -1, Ziv- 4.0 mg kg -1, iv, mg kg -1, ~ 7.0 mg kg -1 ) MTD (dose- limiting toxicities, DLTs, ) 1.0 (RECIST), 4 ( 8 ), Ziv - 1 1, 3 VEGF, (PR), 24 ~ 48 h, 1 ( 63.8% ) Ziv- (36.2%) (27.7%), VEGF Ziv- VEGF ; Ziv- (46.8%) (38.3%) VEGF Ziv- (10.6%), 2.0 ~ 9.0 mg kg % 16.7% 14.3% 57.1%

3 % 61.5%, Ziv- [11, 13-15] mcrc, 3.5 d (1 ~ 21 d) YOSHINO [12] 15 d (14 ~ 16 d) [10],, Ziv- mcrc Ziv- 4.0 mg kg -1,, Ziv-, Ziv- 4.0 mg kg -1, iv, ISAMBERT [11] Ziv-, mcrc, 2008, 54 (96% (7 1 ), 16.7% ), 2012 TANG [16] (n = 34), 1 mcrc (2.0 ~ 9.0 mg kg -1 ) Ziv-, 21 d ; 20, 1 Ziv- 6.0 mg kg -1, iv, 21 d, Ziv- 4.0 mg kg -1, iv, : (83.3%) 2 1, RR PFS, (75.9%) (68.5%), 4 (1 ~ 16 ) 3/4 (18.5%) (16.7%) (24.1%) 54, 7 PR, 32 (stable disease, SD) 1 Ziv- 6 (12.0%), PFS mg kg -1, iv, 21 d [95% (CI): 1.7 ~ 8.6 ] 2.4 Ziv-, (95%CI: 1.9 ~ 3.7 ); OS YOSHINO [12] Ziv- 6.2 ~ 10.6 ) FOLFIRI mcrc, Ziv- ) 55 (74.3%) DLTs, 3/4 10 (13.5%) 8 (10.8%) 5 (6.8%) 5 Ziv mg kg -1, mcrc 3 13, , Ziv- FOLFIRI DLTs,, Ziv- 3/4 4.0 mg kg mg kg -1 12, ( ) ( 4.0 mg kg -1 ) 4.0 mg kg -1 (response 20 (27.0%), rate, RR) (progression- free survival, PFS) 8.3% 7.59, 2, 1, 1, 1 : Ziv- FOLFIRI, 1 ), Ziv- Ziv- FOLFIRI mcrc 4.0 mg kg -1, 2 1 Ziv- mcrc 74, 24, 50 : 24 SD 16 5 (20.8%), 50 PR 1, SD 16 (95%CI: 7.6 ~ 15.5 ) 8.5 (95%CI: ( (6.8%),, mg kg -1 1, 10 (13.5%, 4 (RR 16 PFS), Ziv-

4 695 (19.3% vs. 7.8%) (16.9% vs. 10.6%) ( ) mcrc, Ziv- 6.9%) (36.7% vs. 29.5%), (3.3% vs. 1.7%) (12.1%),, Ziv- 26.8%, Ziv-, VEGFA VEGFB PIGF Ziv-, FOFIRI mcrc 2014 TABERNERO [4] VELOUR [ ( Ziv-, ( VELOUR ) [17] 1 401, mcrc FOLFIRI Ziv- OS 12.5 (95%CI: 10.8 ~ 15.5) vs (95%CI: 9.8 ~ 13.8); (n = 612) FOLFIRI (n = 614),, Ziv- Ziv- OS 13.9 (95%CI: 12.7 ~ 15.6) Ziv- vs (95%CI: 11.2 ~ 13.5), OS 4.0 mg kg -1, iv, 2 1, (P = ) FOLFIRI ( 180 mg m min, 400 mg m -2 2 h, 400 mg m -2, mg m h), 22.28, OS PFS Ziv- 19.8% (95%CI:, 16.4% ~ 23.2% ), 11.1% mcrc, Ziv- (95%CI: 8.5% ~ 13.8%) Ziv-, KRAS OS [13.50 vs ; Ziv-, (HR): 0.817; 95%CI: ~ 0.937; P = ], PFS (6.90 vs ;, HR: 0.758; 95%CI: ~ 0.869; P = ),,, Ziv- mcrc Ziv- 3/, Ziv % 62.5%, 3/4 mcrc 2.9% vs. 1.7% Ziv- 1.8% vs. 0.5% 7.9% vs. 6.3% 3/4 mcrc, Ziv- 19.1%, 1.5%, Ziv- 1 (0.2%) 4, Ziv-, (13.7% vs. 5.0%) (12.3% vs. ) ( )] Ziv-,, Ziv-, Ziv- Ziv- mcrc,, mcrc, 3/4, Ziv- mcrc

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