臨床外科60巻2号

2005年02月発行

特集 再発食道癌を考える

再発食道癌の最近の非手術治療

著者： 才川義朗¹ 小澤壯治¹ 北川雄光¹ 北島政樹¹

所属機関： ¹慶應義塾大学医学部外科

ページ範囲：P.177 - P.185

要旨：再発食道癌の治療には化学・放射線・手術療法などがあるが，本稿では非手術治療について文献的考察を中心に言及する．再発食道癌にはcisplatinを中心とした併用regimenが多く適用とされる．CDDP/5-FUは標準的治療とされ30～50％程の奏効率である．一方taxanesを初めとする新規抗癌剤が開発され，よりよいregimenの確立が期待される．本稿ではdocetaxel，paclitaxel，irinotecan（CPT-11），nedaplatin（CDGP），S-1，gemcitabine，oxaliplatin（L-OHP）などの新規薬剤を含めて再発食道癌治療の現状と将来について考察する．

参考文献

1）The Japanese Society for Esophageal Diseases：Comprehensive registry of esophageal cancer in Japan（1995, 1996, 1997）. 2nd ed, 2000

2）Hanashi T：Clinical evaluation on treatments for mucosal cancer of esophagus. Disease of the Esophagus. 1996, pp203-207

3）Ando N, Ozawa S, Kitagawa Y, et al：Improvement in the result of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg 232：225-232, 2000

4）Swisher SG, Ajani JA, Komaki R, et al：Long-term outcome of phaseⅡtrial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer. Int J Radiat Oncol Biol Phys 57：120-127, 2003

5）Ross PJ, Rao S, Cunningham D：Chemotherapy of oesophago-gastric cancer. Pathol Oncol Res 4：87-95, 1998

6）Enzinger PC, Ilson DH, Kelsen DP：Chemotherapy in esophageal cancer. Semin Oncol 26：12-20, 1999

7）Shah MA, Schwartz GK：Treatment of metastatic esophagus and gastric cancer. Semin Oncol 31：574-587, 2004

8）Ajani JA：Current status of new drugs and multidisciplinary approaches in patients with carcinoma of the esophagus. Chest 113：S112-S119, 1998

9）安藤暢敏，石　志紘：食道癌の化学療法．日外会誌103：359-363，2002

10）北川雄光，小澤壯治，北島政樹：食道癌の治療に関する最新データ．臨外（増）57：113-121，2002

11）Ilson DH, Kelsen DP：Combined modality therapy in the treatment of esophageal cancer. Semin Oncol 21：493-507, 1994

12）Ando N, Iizuka T, Ide H, et al：A randomized trial of surgery alone vs surgery plus postoperative chemotherapy with cisplatin and 5-fluorouracil for localized squamous carcinoma of the thoracic esophagus：the Japan Clinical Oncology Group Study（JCOG 9204）. Proc Am Soc Clin Oncol：269a, 1999

13）Kok TC, Van der Gaast A, et al：Cisplatin and etoposide in oesophageal cancer；a phaseⅡstudy. Rotterdam Oesophageal Tumour Study Group. Br J Cancer 74：980-984, 1996

14）Spiridonidis CH, Laufman LR, Jones JJ, et al：A phaseⅡevaluation of high dose cisplatin and etoposide in patients with advanced esophageal adenocarcinoma. Cancer 78：2070-2077, 1996

15）Stewart FM, Harkins BJ, Hahn SS, et al：Cisplatin, 5-fluorouracil, mitomycin C, and concurrent radiation therapy with and without esophogectomy for esophageal carcinoma. Cancer 64：622-628, 1989

16）Iizuka T, Kakegawa T, Ide H, et al：PhaseⅡevaluation of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus；a Japanese Esophageal Oncology Group Trial. Jpn J Clin Oncol 22：172-176, 1992

17）Ilson DH, Sirott M, Saltz L, et al：A phaseⅡtrial of interferon alpha-2A, 5-fluorouracil, and cisplatin in patients with advanced esophageal carcinoma. Cancer 75：2197-2202, 1995

18）Bamias A, Hill ME, Cunningham D, et al：Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for esophagogastric adenocarcinoma；response, toxicity, quality of life, and survival. Cancer 77：1978-1985, 1996

19）Wadler S, Haynes H, Beitler JJ, et al：PhaseⅡclinical trial with 5-fluorouracil, recombinant interferon-alpha-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus. Cancer 78：30-34, 1996

20）Feliu J, Gonzalez Baron M, Garcia Giron C, et al：PhaseⅡstudy of cisplatin, 5-fluorouracil, and leucovorin in inoperable squamous cell carcinoma of the esophagus. ONCOPAZ Cooperative Group, Spain. Am J Clin Oncol 19：577-580, 1996

21）Bleiberg H, Conroy T, Paillot B, et al：Randomised phaseⅡstudy of cisplatin and 5-fluorouracil（5-FU）versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer 33：1216-1220, 1997

22）Steyn RS, Vijeyasingam R, Darnton SJ, et al：A phaseⅡtrial of cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus. Clin Oncol（R Coll Radiol）10：170-172, 1998

23）Warner E, Jensen JL, Cripps C, et al：Outpatient 5-fluorouracil, folinic acid and cisplatin in patients with advanced esophageal carcinoma. Acta Oncol 38：255-259, 1999

24）Sekiguchi H, Akiyama S, Fujiwara M, et al：PhaseⅡtrial of 5-fluorouracil and low-dose cisplatin in patients with squamous cell carcinoma of the esophagus. Surg Today 29：97-101, 1999

25）Hayashi K, Ando N, Watanabe H, et al：PhaseⅡevaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus；a Japan Esophageal Oncology Group（JEOG）Trial（JCOG9407）. Jpn J Clin Oncol 31：419-423, 2001

26）Polee MB, Kok TC, Siersema PD, et al：PhaseⅡstudy of the combination cisplatin, etoposide, 5-fluoro-uracil and folinic acid in patients with advanced squamous cell carcinoma of the esophagus. Anticancer Drugs 12：513-517, 2001

27）Nishimura Y, Koike R, Nakamatsu K, et al：Concurrent chemoradiotherapy with protracted infusion of 5-FU and cisplatin for postoperative recurrent or residual esophageal cancer. Jpn J Clin Oncol 33：341-345, 2003

28）Iwase H, Shimada M, Nakamura M, et al：Concurrent chemoradiotherapy for locally advanced and metastatic esophageal cancer；longterm results of a phaseⅡstudy of UFT/CDDP with radiotherapy. Int J Clin Oncol 8：305-311, 2003

29）Hsu CH, Cheng AL, Hsu C, et al：A phaseⅡstudy of weekly methotrexate, cisplatin, and 24-hour infusion of high-dose 5-fluorouracil and leucovorin（MP-HDFL）in patients with metastatic and recurrent esophageal cancer-improving toxicity profile by infusional schedule and double biochemical modulation of 5-fluorouracil. Anticancer Res 22：3621-3627, 2002

30）Ajani JA, Ilson DH, Daugherty K, et al：Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst 86：1086-1091, 1994

31）Ajani JA, Ilson DH, Daugherty K, et al：Paclitaxel in the treatment of carcinoma of the esophagus. Semin Oncol 22：35-40, 1995

32）Ajani JA, Ilson DH, Kelsen DP：Paclitaxel in the treatment of patients with upper gastrointestinal carcinomas. Semin Oncol 23：55-58, 1996

33）Ilson DH, Ajani J, Bhalla K, et al：PhaseⅡtrial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. J Clin Oncol 16：1826-1834, 1998

34）Petrasch S, Welt A, Reinacher A, et al：Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. Br J Cancer Aug 78：511-514, 1998

35）Lokich JJ, Sonneborn H, Anderson NR, et al：Combined paclitaxel, cisplatin, and etoposide for patients with previously untreated esophageal and gastroesophageal carcinomas. Cancer 85：2347-2351, 1999

36）Weiner LM：Paclitaxel in the treatment of esophageal cancer. Semin Oncol 26：106-108, 1999

37）Anderson SE, O'Reilly EM, Kelsen DP, et al：PhaseⅡtrial of 96-hour paclitaxel in previously treated patients with advanced esophageal cancer. Cancer Invest 21：512-516, 2003

38）El-Rayes BF, Shields A, Zalupski M, et al：A phaseⅡstudy of carboplatin and paclitaxel in esophageal cancer. Ann Oncol 15：960-965, 2004

39）Polee MB, Sparreboom A, Eskens FA, et al：A phaseⅠand pharmacokinetic study of weekly paclitaxel and carboplatin in patients with metastatic esophageal cancer. Clin Cancer Res 10：1928-1934, 2004

40）Einzig AI, Neuberg D, Remick SC, et al：PhaseⅡtrial of docetaxel（Taxotere）in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy；the Eastern Cooperative Oncology Group（ECOG）results of protocol E1293. Med Oncol 13：87-93, 1996

41）Heath EI, Urba S, Marshall J, et al：PhaseⅡtrial of docetaxel chemotherapy in patients with incurable adenocarcinoma of the esophagus. Invest New Drugs 20：95-99, 2002

42）Bleickardt E, Argiris A, Rich R, et al：PhaseⅠdose escalation trial of weekly docetaxel plus irinotecan in patients with advanced cancer. Cancer Biol Ther 1：646-651, 2002

43）Jatoi A, Tirona MT, Cha SS, et al：A phaseⅡtrial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia. Int J Gastrointest Cancer 32：115-123, 2002

44）Govindan R, Read W, Faust J, et al：PhaseⅡstudy of docetaxel and irinotecan in metastatic or recurrent esophageal cancer；a preliminary report. Oncology（Huntingt）17：27-31, 2003

45）Lordick F, von Schilling C, Bernhard H, et al：PhaseⅡtrial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer. Br J Cancer 89：630-633 2003

46）Airoldi M, Cortesina G, Giordano C, et al：Docetaxel and vinorelbine；an effective regimen in recurrent squamous cell esophageal carcinoma. Med Oncol 20：19-24, 2003

47）Muro K, Hamaguchi T, Ohtsu A, et al：A phaseⅡstudy of single-agent docetaxel in patients with metastatic esophageal cancer. Ann Oncol 15：955-959, 2004

48）Maeda S, Saikawa Y, Kubota T, et al：No cross-resistance of taxotere and taxol to conventional chemotherapeutic agents against gastric cancers as detected by MTT assay. Anticancer Res 23：3147-3150, 2003

49）Maeda S, Sugiura T, Saikawa Y, et al：Docetaxel will enhance the cytotoxicity of cisplatin against gastric cancer cells via modification of multidrug resistance-associated protein-1 expression. Cancer Sci 95：679-684, 2004

50）Ilson DH, Saltz L, Enzinger P, et al：PhaseⅡtrial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol 17：3270-3275, 1999

51）Ajani JA, Baker J, Pisters PW, et al：CPT-11 plus cisplatin in patients with advanced, untreated gastric or gastroesophageal junction carcinoma；results of a phaseⅡstudy. Cancer 94：641-646, 2002

52）Ilson DH, Minsky B, Kelsen D：Irinotecan, cisplatin, and radiation in esophageal cancer. Oncology（Huntingt）16：11-15, 2002

53）Assersohn L, Brown G, Cunningham D, et al：PhaseⅡstudy of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Ann Oncol 15：64-69, 2004

54）Muro K, Ando N, Nishimaki T, et al：A phaseⅡstudy of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus；Japan Clinical Oncology Group study（JCOG 9905）. Proc ASCO 22：277, 2003

55）Kato H, Fukuchi M, Manda R, et al：Efficacy and toxicity of nedaplatin and 5-FU with radiation treatment for advanced esophageal carcinomas. Anticancer Res 23：3493-3498, 2003

56）Yoshioka T, Gamoh M, Shineha R, et al：A new combination chemotherapy with cis-diammine-glycolatoplatinum（Nedaplatin）and 5-fluorouracil for advanced esophageal cancers. Intern Med 38：844-848, 1999

57）Hirao M, Fujitani K, Tsujinaka T：PhaseⅠstudy of the combination of nedaplatin, adriamycin and 5-fluorouracil for treatment of advanced esophageal cancer. Dis Esophagus 17：247-250, 2004

58）Fukushima M, Shimamoto Y, Kato T, et al：Anticancer activity and toxicity of S-1, an oral combination of tegafur and two biochemical modulators, compared with continuous i.v. infusion of 5-fluorouracil. Anticancer Drugs 9：817-823, 1998

59）Hirata K, Horikoshi N, Aiba K, et al：Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug. Clin Cancer Res 5：2000-2005, 1999

60）Koizumi W, Kurihara M, Nakano S, et al：PhaseⅡstudy of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer―For the S-1 Cooperative Gastric Cancer Study Group. Oncology 58：191-197, 2000

61）Sugimachi K, Maehara Y, Horikoshi N, et al：An early phaseⅡstudy of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group. Oncology 57：202-210, 1999

62）Koizumi W, Tanabe S, Saigenji K, et al：PhaseⅠ/Ⅱstudy of S-1 combined with cisplatin in patients with advanced gastric cancer. Br J Cancer 89：2207-2212, 2003

63）Saikawa Y, Akasaka Y, Kanai T, et al：Preoperative combination chemotherapy with S-1 and low dose cisplatin against highly advanced gastric cancer. Oncol Rep 10：381-386, 2003

64）Oettle H, Arnold D, Kern M, et al：PhaseⅠstudy of gemcitabine in combination with cisplatin, 5-fluorouracil and folinic acid in patients with advanced esophageal cancer. Anticancer Drugs 13：833-838, 2002

65）Kroep JR, Pinedo HM, Giaccone G, et al：PhaseⅡstudy of cisplatin preceding gemcitabine in patients with advanced oesophageal cancer. Ann Oncol 15：230-235, 2004

66）Urba SG, Chansky K, VanVeldhuizen PJ, et al：Gemcitabine and cisplatin for patients with metastatic or recurrent esophageal carcinoma；a Southwest Oncology Group Study. Invest New Drugs 22：91-97, 2004

67）Sandler AB, Kindler HL, Einhorn LH, et al：PhaseⅡtrial of gemcitabine in patients with previously untreated metastatic cancer of the esophagus or gastroesophageal junction. Ann Oncol 11：1161-1164, 2000

68）Khushalani NI, Leichman CG, Proulx G, et al：Oxaliplatin in combination with protracted-infusion fluorouracil and radiation；report of a clinical trial for patients with esophageal cancer. J Clin Oncol 20：2844-2850, 2002

69）Richard MG, et al：Oxaliplatin（Oxal）or CPT-11＋5-fluorouracil（5FU）/leucovorin（LV）or oxal＋CPT-11 in advanced colorectal cancer（CRC）. Update efficacy and quality of life（QOL）data from an intergroup study. Proceeding of ASCO 2003, p252, 2003

70）Hoff PM, Fuchs CS：The experience with oxaliplatin in the treatment of upper gastrointestinal carcinomas. Semin Oncol 30：54-61, 2003

71）Demetri DD, von Mehren M, Blanke CD, et al：Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347：472-480, 2002

72）Yamazaki M, Yamashita Y, Kubo N, et al：Effect of trastuzumab for human esophageal cancer. Gan To Kagaku Ryoho 30：1780-1783, 2003

73）Ilson DH, Minsky B：Irinotecan in esophageal cancer. Oncology（Huntingt）17：32-36, 2003

74）Gupta VK, Park JO, Kurihara T, et al：Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model. Gene Ther 10：206-2012, 2003