臨床外科65巻4号

2010年04月発行

特集 消化器癌neoadjuvant chemotherapyの新展開 〔切除不能例に対するdown-staging〕

切除困難大腸癌肝転移に対するdown-staging chemotherapy後の外科切除

著者： 吉留博之¹ 木村文夫¹ 清水宏明¹ 大塚将之¹ 加藤厚¹ 古川勝規¹ 吉富秀幸¹ 竹内男¹ 高屋敷吏¹ 須田浩介¹ 久保木知¹ 高野重紹¹ 宮崎勝¹

所属機関： ¹千葉大学大学院医学研究院臓器制御外科・肝胆膵外科

ページ範囲：P.522 - P.527

要旨：切除不能と判断される大腸癌肝転移症例は未だ多く存在するが，最近の新規抗癌剤ならびに分子標的治療剤の飛躍的進歩により，術前に投与することで切除可能へとconvertする治療戦略の報告がなされるようになってきた．切除可能となれば，その予後は切除可能肝転移症例と遜色がなく有効な治療戦略と考えられる．一方，抗癌剤による肝障害の問題や抗腫瘍効果の点からも明確にすべき点が多く残されている．本稿では投与する抗癌剤・分子標的治療剤の種類とその成績を，自験例と文献的考察を含めて詳述した．

参考文献

1）Saltz LB, Cox JV, Blanke C, et al：Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343：905-914, 2000

2）de Gramont A, Figer A, Seymour M, et al：Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18：2938-2947, 2000

3）Grothey A, Deschler B, Kroening H, et al：Phase Ⅲ study of bolus 5-fluorouracil（5-FU）/folinic acid（FA）（Mayo）vs. weekly high-dose 24h 5-FU infusion/FA＋oxaliplatin（OXA）in advanced colorectal cancer（ACRC）. Proc Am Soc Clin Oncol 21：129a, 2002（abstr #512）

4）Goldberg RM, Sargent DJ, Morton RF, et al：A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22：23-30, 2004

5）Tournigand C, André T, Achille E, et al：FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer：a randomized GERCOR study. J Clin Oncol 22：229-237, 2004

6）Hurwitz H, Fehrenbacher L, Novotny W, et al：Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350：2335-2342, 2004

7）Saltz LB, Clarke S, Díaz-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 Clin Oncol 26：2013-2019, 2008

8）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 Clin Oncol 26：2311-2319, 2008

9）Van Cutsem E, Köhne CH, Hitre E, et al：Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360：1408-1417, 2009

10）Adam R, Delvart V, Pascal G, et al：Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy：a model to predict long-term survival. Ann Surg 240：644-657, 2004

11）Azoulay D, Castaing D, Smail A, et al：Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Ann Surg 231：480-486, 2000

12）Adam R, Laurent A, Azoulay D, et al：Two-stage hepatectomy：A planned strategy to treat irresectable liver tumors. Ann Surg 32：777-785, 2000

13）Hemming AW, Reed AI, Langham MR Jr, et al：Combined resection of the liver and inferior vena cava for hepatic malignancy. Ann Surg 239：712-719, 2004

14）Miyazaki M, Ito H, Nakagawa K, et al：Aggressive surgical resection for hepatic metastases involving the inferior vena cava. Am J Surg 177：294-298, 1999

15）Bismuth H, Adam R, Lévi F, et al：Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 224：509-520, 1996

16）Lévi F, Zidani R, Misset JL：Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lancet 350：681-686, 1997

17）Adam R, Avisar E, Ariche A, et al：Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol 8：347-353, 2001

18）Pozzo C, Basso M, Cassano A, et al：Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients. Ann Oncol 15：933-939, 2004

19）Alberts SR, Horvath WL, Sternfeld WC, et al：Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer：a North Central Cancer Treatment Group phase Ⅱ study. J Clin Oncol 23：9243-9249, 2005

20）Capussotti L, Muratore A, Mulas MM, et al：Neoadjuvant chemotherapy and resection for initially irresectable colorectal liver metastases. Br J Surg 93：1001-1006, 2006

21）Zorzi D, Laurent A, Pawlik TM, et al：Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg 94：274-286, 2007

22）Vauthey JN, Pawlik TM, Ribero D, et al：Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24：2065-2072, 2006

23）Karoui M, Penna C, Amin-Hashem M, et al：Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg 243：1-7, 2006

24）Ribero D, Wang H, Donadon M, et al：Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110：2761-2767, 2007

25）Benoist S, Brouquet A, Penna C, et al：Complete response of colorectal liver metastases after chemotherapy：does it mean cure? J Clin Oncol 24：3939-3945, 2006

26）Yoshidome H, Kimura F, Shimizu H, et al：Interval period tumor progression：does delayed hepatectomy detect occult metastases in synchronous colorectal liver metastases? J Gastrointest Surg 12：1391-1398, 2008