臨床外科64巻7号

2009年07月発行

特集 肝胆膵癌に対する補助療法―治療成績の向上を目指して

膵癌に対する補助療法の有用性

著者： 坂本快郎¹ 高森啓史¹ 田中洋¹ 中原修¹ 橋本大輔¹ 赤星慎一¹ 尾崎宣之¹ 古橋聡¹ 馬場秀夫¹

所属機関： ¹熊本大学大学院医学薬学研究部消化器外科学

ページ範囲：P.925 - P.932

要旨：膵癌は切除率が低く，さらに根治切除術後でも高率に再発を認める予後不良な疾患である．膵癌の予後向上のために有効な補助療法の確立が試みられている．近年，gemcitabine（GEM）による術後補助療法に関する無作為化比較試験においてその有用性が報告された．一方，術前補助療法に関してはいくつかの報告はあるものの，無作為化比較試験による十分なエビデンスは得られておらず，これからの課題である．

参考文献

1）田中雅夫：膵癌全国登録調査報告．膵臓 22：e1-e427，2007

2）Yeo CJ, Cameron JL, Lillemoe KD, et al：Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 221：721-731, 1995

3）American Cancer Society：Cancer Facts and Figures 2008. http//www.cancer.org

4）厚生労働省：平成19年度人口動態調査．http://www.mhjw.go.jp/toukei/list/81-1.html

5）Pedrazzoli S, DiCarlo V, Dionigi R, et al：Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas：a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg 228：508-517, 1998

6）Yeo CJ, Cameron JL, Lillemoe KD, et al：Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2：randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 236：355-366, 2002

7）Farnell MB, Pearson RK, Sarr MG, et al：A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery 138：618-628, 2005

8）Nimura Y, Nagino M, Kato H et al：Regional versus extended lymph nodedissection in radical pancreatoduodenectomy for pancreatic cancer：a multicenter, randomized controlled trial. HPB Off J Int Hepato Pancreato Biliary Assoc 6：2, 2004

9）Griffin JF, Smalley SR, Jewell W, et al：Patterns of failure after curative resection of pancreatic carcinoma. Cancer 66：56-61, 1990

10）Sperti C, Pasquali C, Piccoli A, et al：Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg 21：195-200, 1997

11）Kalser MH, Ellenberg SS：Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120：899-903, 1985

12）Gastrointestinal Tumor Study Group：Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59：2006-2010, 1987

13）Klinkenbijl JH, Jeekel J, Sahmoud T, et al：Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region：phase Ⅲ trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230：776-782, 1999

14）Neoptolemos JP, Stocken DD, Friess H, et al：A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350：1200-1210, 2004

15）Stocken DD, Buchler MW, Dervenis C, et al：Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer 92：1372-1381, 2005

16）Takada T, Amano H, Yasuda H, et al：Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase Ⅲ multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95：1685-1695, 2002

17）Kosuge T, Kiuchi T, Mukai K, et al：A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol 36：159-165, 2006

18）Burris HA 3rd, Moore MJ, Andersen J, et al：Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer：a randomized trial. J Clin Oncol 15：2403-2413, 1997

19）Oettle H, Post S, Neuhaus P, et al：Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer：a randomized controlled trial. JAMA 297：267-277, 2007

20）Neuhaus P, Riess H, Post S, et al：CONKO-001：Final results of the randomized, prospective, multicenter phase Ⅲ trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer（PC）. J Clin Oncol 26：LBA4504（Meeting Abstracts）, 2008

21）Kosuge T, Ueno H, Matsuyama Y, et al：A randomized phase Ⅲ study comparing gemcitabinemonotherapy with observation in patients with resectedpancreatic cancer. Eur J Cancer（ECCO14 Abstract Book；abstract 3504）, 2007

22）Regine WF, Winter KW, Abrams R, et al：RTOG 9704 a phase Ⅲ study of adjuvant pre and post chemoradiation（CRT）5-FU vs. gemcitabine（G）for resected pancreatic adenocarcinoma. J Clin Oncol 24：4007（Meeting Abstracts）. 2006

23）Regine WF, Winter KA, Abrams RA, et al：Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma：a randomized controlled trial. JAMA 299：1019-1026, 2008

24）Neoptolemos JP, Stocken DD, Tudur Smith C, et al：Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer：composite data from the ESPAC-1 and-3（v1）trials. Br J Cancer 100：246-250, 2009

25）Maeda A, Boku N, Fukutomi A, et al：Randomized phase Ⅲ trial of adjuvant chemotherapy with gemcitabine versus S-1 in patients with resected pancreatic cancer：Japan Adjuvant Study Group of Pancreatic Cancer（JASPAC-01）. Jpn J Clin Oncol 38：227-229, 2008

26）Murakami Y, Uemura K, Sudo T, et al：Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 195：757-762, 2008

27）Sohn TA, Yeo CJ, Cameron JL, et al：Resected adenocarcinoma of the pancreas-616 patients：results, outcomes, and prognostic indicators. J Gastrointest Surg 4：567-579, 2000

28）Mornex F, Girard N, Delpero JR, et al：Radiochemotherapy in the management of pancreatic cancer―part Ⅰ：neoadjuvant treatment. Semin Radiat Oncol 15：226-234, 2005

29）Tse RV, Dawson LA, Wei A, et al：Neoadjuvant treatment for pancreatic cancer―a review. Crit Rev Oncol Hematol 65：263-274, 2008

30）Evans DB, Rich TA, Byrd DR, et al：Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 127：1335-1339, 1992

31）Yeung RS, Weese JL, Hoffman JP, et al：Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase Ⅱ Study. Cancer 72：2124-2133, 1993

32）Staley CA, Lee JE, Cleary KR, et al：Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Am J Surg 171：118-124, 1996

33）Spitz FR, Abbruzzese JL, Lee JE, et al：Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 15：928-937, 1997

34）Pisters PW, Abbruzzese JL, Janjan NA, et al：Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol 16：3843-3850, 1998

35）Breslin TM, Hess KR, Harbison DB, et al：Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas：treatment variables and survival duration. Ann Surg Oncol 8：123-132, 2001

36）Pisters PW, Wolff RA, Janjan NA, et al：Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma：toxicities, histologic response rates, and event-free outcome. J Clin Oncol 20：2537-2544, 2002

37）Hoffman JP, Lipsitz S, Pisansky T, et al：Phase Ⅱ trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas：an Eastern Cooperative Oncology Group Study. J Clin Oncol 16：317-323, 1998

38）Sasson AR, Wetherington RW, Hoffman JP, et al：Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas：analysis of histopathology and outcome. Int J Gastrointest Cancer 34：121-128, 2003

39）Moutardier V, Magnin V, Turrini O, et al：Assessment of pathologic response after preoperative chemoradiotherapy and surgery in pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 60：437-443, 2004

40）Mornex F, Girard N, Scoazec JY, et al：Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma：The French SFRO-FFCD 97-04 Phase Ⅱ trial. Int J Radiat Oncol Biol Phys 65：1471-1478, 2006

41）White RR, Xie HB, Gottfried MR, et al：Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. Ann Surg Oncol 12：214-221, 2005

42）Talamonti MS, Small W, Jr, Mulcahy MF, et al：A multi-institutional phase Ⅱ trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol 13：150-158, 2006

43）Palmer DH, Stocken DD, Hewitt H, et al：A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer：gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol 14：2088-2096, 2007

44）Evans DB, Varadhachary GR, Crane CH, et al：Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26：3496-3502, 2008

45）Varadhachary GR, Wolff RA, Crane CH, et al：Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26：3487-3495, 2008

46）Takamori H, Kanemitsu K, Chikamoto A, et al：A novel multimodality treatment for resectable pancreatic cancer（PC）. J Clin Oncol 25：4630（meeting abstracts）, 2007

47）Brunner TB, Grabenbauer GG, Meyer T, et al：Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomised phase Ⅱ-study of the Interdisciplinary Working Group Gastrointestinal Tumours（AIO, ARO, and CAO）. BMC Cancer 7：41, 2007

48）Moore MJ, Goldstein D, Hamm J, et al：Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer：a phase Ⅲ trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25：1960-1966, 2007

49）Vervenne W, Bennouna J, Humblet Y, et al：A randomized, double-blind, placebo（P）controlled, multicenter phase Ⅲ trial to evaluate the efficacy and safety of adding bevacizumab（B）to erlotinib（E）and gemcitabine（G）in patients（pts）with metastatic pancreatic cancer. J Clin Oncol 26：4507（meeting abstracts）, 2008

50）Cutsem EV, Vervenne WL, Bennouna J, et al：Rash as a marker for the efficacy of gemcitabine plus erlotinib-based therapy in pancreatic cancer. Results from the AViTA study. Gastrointestinal Cancers Symposium abstract #117, 2009