繼續教育 大腸癌各分期的藥物治療 成功大學附設醫院藥劑部藥師陳弘益 摘要 15-30%50-60% 5-fluororuracil oxaliplatin irinotecan bevacizumab (Avastin) aflibercept (Zaltrap, ) -cetuximab (Erbitux) panitumumab (Vectibix) regorafenib colorectal cancerpharmacotherapy 臨床藥Therapeutics of Clinical Drugs 物治療學壹 前言 2011 (Colorectal cancer, CRC) 15.2% 1,2 15-30%50-60% 3 5 94-97% 5 5% 4 19945-fluororuracil (5-FU) 5-FU oxaliplatin irinotecan 68 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.4 Dec. 31 2015 (Vascular endothelial growth factor, VEGF) aflibercept (Zaltrap) bevacizumab (Avastin) (epidermal growth factor receptor, EGFR) -cetuximab (Erbitux, ) panitumumab (Vectibix, ) 5 Regorafenib 6 貳 癌症分期
(American Joint Committee on Cancer) TNM (Tumor node metastasis, TNM) () 7,8 2014 Pocket Medicine The Massachusetts General Hospital Handbook of Internal Medicine (Pocket Notebook) 94-97% 56-83% 15-86%5% 4 5 86% 81%72% 57% 12% 56%65% 9 5-FU leucovorin cisplatin 11 5 10 表一大腸癌之分期 -TNM (T 描述腫瘤大小 N 描述淋巴腺轉移 M 描述遠處轉移 ) 11 Tis T1 T2 T3 T4 T4a N1 T4b 1~3 N1a N1b N1c 1 2-3 臨床藥物治療學N2 4 N2a 4-6 N2b 7 M1 M1a M1b 11 表二各種分期對照表 Stage T N M 0 Tis N0 M0 I T1 N0 M0 T2 N0 M0 IIA T3 N0 M0 IIB T4a N0 M0 IIC T4b N0 M0 IIIA T1-T2 N1 M0 T1 N2a M0 T3-T4a N1/N1c M0 IIIB T2-T3 N2a M0 T1-T2 N2b M0 T4a N2a M0 IIIC T3-T4a N2b M0 T4b N1-N2 M0 IVA Any T Any N M1a IVB Any T Any N M1b 參 以分期為基礎的藥物治療 ( 表三 ) 表三以分期為基礎的藥物治療 I IIA 1.5- IIB FU leucovorin (LV) 2.FOLFOX IIC (5-FU+leucovorin+oxaliplatin) 3.capecitabine 314 Dec. 31 2015 藥學雜誌 125 69
繼續教育 臨床藥Therapeutics of Clinical Drugs 物治療學 IIIA 1.FOLFOX IIIB 2.FLOX (5-FU+oxaliplatin) 3.XELOX (capecitabine+oxaliplatin) 4.5-FU+LV IIIC 5.tegafur-uracil 1. IV 2. (isolated metastasis) 3. 5-FU+LV+ bevacizumab FOLFOX FOLFIRI bevacizumab cetuximab panitumumab 4. FOLFIRI aflibercept panitumumab IV 5. regorafenib FOLFIRI+(bevacizumab cetuximab) FOLFOX+ (bevacizumab cetuximab) aflibercept panitumumab regorafenib 2015 NCCN guideline 12 (Carcinoembryonic antigen, CEA) 5 ng/ml T4 5 3 (1) 5-FU leucovorin (LV) (2) FOLFOX (5-FU+leucovorin+oxaliplatin) 70 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.4 Dec. 31 2015 (3) capcitabine 5-FU LV FOLFOX FOLFOX FOLFOX 41.1%5-FU+LV 4.7% (HR 0.8, 95% CI, 0.56-1.15) (FOLFOX 87% 5-FU+LV 84.3%) 13 5-FU (1) FOLFOX (2) FLOX (5-FU+oxaliplatin) (3) XELOX (capcitabine+oxaliplatin) (4) 5-FU+LV (5) tegafur-uracil 3,8 2015 NCCN guideline FOLFOX 5-FU+LV bevacizumab aflibercept) cetuximab panitumumab regorafenib regorafenib 5-FU oxaliplatin irinotecan (Interstitial Fluid Pressure, IFP IFP IFP
藥學雜誌 125 71 表四大腸直腸癌治療藥品組合比較 ( ) 1 2004 2007 2007 irinotecan 2008 2010 臨床藥物治療學 314 Dec. 31 2015 IFL+B v.s. IFL 20.3 v.s.15.6 10.6 v.s. 6.2 45% v.s.35% 74% v.s.63% B N Engl J Med 2004; 350:2335-2342. FOLFIRI +B v.s. mifl+b 28 v.s.19 11 v.s.8 58% v.s.53% 87% v.s.61% 5-FU (FOLFIRI) (IFL) FOXFOX-4+B v.s. FOXFOX v.s. B FOXFOX-4 XELOX+B v.s.foxfox-4 XELOX cape v.s. cape+b v.s. cape+b+mitomycin 2011KRAS exon FOLFOX/XELOX v.s. 2 wild-type FOLFOX/XELOX+C 2012 oxaliplatin B 2013 2013 2013 +B FOLFIRI+aflibercept v.s. FOLFIRI+ 12.9 v.s.10.8 v.s.10.2 7.3 v.s.4.7 v.s.2.7 22.7% v.s.8.6% v.s.3.3% 56% v.s.43% v.s.44% B 21.3 v.s.19.9 9.4 v.s.8.0 47% v.s.49% B 18.9 v.s.18.9 v.s.16.4 5.7 v.s.8.5 v.s.8.4 30% v.s.38% v.s.46% B cape 17.9 v.s. 17.0 8.6v.s.8.6 57% v.s.64% C oxaliplatin 13.5 v.s.12.0 6.9 v.s.4.7 20% v.s.11% 56% v.s.50% FOLFIRI aflibercept 12.0613.5 cape v.s. cape+b 20.7 v.s.16.8 9.1 v.s.5.1 19% v.s.10% 74% v.s.44% B cape FOLFOXIRI+B v.s. FOLFIRI+B +B v.s. 2014KRAS exon FOLFIRI+C v.s. 2 wild-type FOLFIRI+B 2014KRAS exon FOLFIRI 2 wild-type +P v.s. FOLFIRI 31.0 v.s.25.8 12.1 v.s.9.7 65% v.s.53% FOLFOXIRI+B 11.2 v.s.9.8 5.7 v.s.4.1 5.5% v.s.4% +B N Engl J Med 2004; 350:2335-2342. J Clin Oncol 2007; 25: 1539-1544. J Clin Oncol 2008; 26: 2013-2019. J Clin Oncol 2010; 28: 3191-3198. Lancet. 2011;377(9783):2103-14. J Clin Oncol 2012; 30:3499-3506. Lancet Oncol 2013; 14: 1077-1085. ASCO Meeting Abstracts 2013; 31: 3505 Lancet Oncol 2013; 14:29-37 28.7 v.s. 25.0 10.0 v.s.10.3 62% v.s. 58% FOLFIRI Lancet Oncol. + C 2014;15(10):1065-75. KRAS exon 2 wild-type FOLFIRI + C 14.5 v.s.12.5 6.7 v.s.4.9 10% v.s. 36% FOLFIRI +P Ann Oncol. 2014;25(1):107-16. IFL = irinotecan + 5-FU + LV FOLFIRI = irinotecan + 465-FU+LV FOLFOX = leucovorin (Folinic acid) + 5-FU + oxaliplatin FOLFOXIRI = leucovorin (Folinic acid) + 5-FU + oxaliplatin + irinotecan B = bevacizumab XELOX = capecitabine (xeloda) + oxaliplatin cape = capecitabine C= cetuximab P = panitumumab 14 () 5-FU bevacizumab 5-FU+bevacizumab 9.2 5-FU 5.5 capecitabine+bevacizumab 8.5 capecitabine 5.7 capecitabine bevacizumab capecitabine capecitabine bevacizumab capecitabine 10
繼續教育 Therapeutics of Clinical Drugs 臨床藥物治療學72 THE JOURNAL OF TAIWAN PHARMACY Vol.31 No.4 Dec. 31 2015 (1) bevacizumab (2) Bevacizumab FOLFOX FOLFIRI FOLFOXIRI bevacizumab 1.4-3.9 K-ras exon 2 wild-type FOLFIRI+cetuximab FOLFIRI+bevacizumab K-ras FOLFIRI+panitumumab FOLFIRI 肆 結果與討論 2014 bevacizumab irinotecan/5-fluorouracil/ leucovorin 5-fluorouracil/leucovorin 24 FOLFOX FOLFOXIRI bevacizumab cetuximab FOLFIRI (Folinic acid/5-fluorouracil/irinotecan) (EGFR expressing) K-ras FOLFIRI cetuximab cetuximab oxaliplatin ( FOLFOX) FOLFOX bevacizumab cetuximab 31 ( K-ras ) 15 Pharmacotherapy of Colon Cancer in Each Stage Hung-Yi Chen Department of Pharmacy, National Cheng Kung University Hospital Abstract More than a half of patients have stage II (T34N0M0) or stage III (TxN1M0) colorectal cancer at the time of diagnosis. Approximately 15-30% of patients with stage II and 50-60%
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