Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer

被引:325
作者
Ebata, T. [1 ]
Hirano, S. [4 ]
Konishi, M. [6 ]
Uesaka, K. [7 ]
Tsuchiya, Y. [9 ]
Ohtsuka, M. [10 ]
Kaneoka, Y. [11 ]
Yamamoto, M. [12 ]
Ambo, Y. [5 ]
Shimizu, Y. [2 ]
Ozawa, F. [13 ]
Fukutomi, A. [8 ]
Ando, M. [3 ]
Nimura, Y. [1 ]
Nagino, M. [1 ]
机构
[1] Nagoya Univ, Div Surg Oncol, Dept Surg, Grad Sch Med, Nagoya, Aichi, Japan
[2] Aichi Canc Ctr Hosp, Dept Gastroenterol Surg, Nagoya, Aichi, Japan
[3] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Nagoya, Aichi, Japan
[4] Hokkaido Univ, Dept Gastroenterol Surg 2, Grad Sch Med, Sapporo, Hokkaido, Japan
[5] Teine Keijinkai Hosp, Dept Surg, Sapporo, Hokkaido, Japan
[6] Natl Canc Ctr Hosp East, Dept Hepatobiliary Pancreat Surg, Kashiwa, Chiba, Japan
[7] Shizuoka Canc Ctr Hosp, Div Hepatobiliary Pancreat Surg, Shizuoka, Japan
[8] Shizuoka Canc Ctr Hosp, Div Gastrointestinal Oncol, Shizuoka, Japan
[9] Niigata Canc Ctr Hosp, Dept Surg, Niigata, Japan
[10] Chiba Univ, Grad Sch Med, Dept Gen Surg, Chiba, Japan
[11] Ogaki Municipal Hosp, Dept Surg, Ogaki, Japan
[12] Tokyo Womens Med Univ, Inst Gastroenterol, Dept Surg, Tokyo, Japan
[13] Saitama Med Univ, Dept Hepatobiliary Pancreat Surg, Saitama Med Ctr, Saitama, Japan
关键词
BILIARY-TRACT CANCER; PERIHILAR CHOLANGIOCARCINOMA; HILAR CHOLANGIOCARCINOMA; PANCREATIC-CANCER; R0; RESECTION; DISTAL CHOLANGIOCARCINOMA; CURATIVE-INTENT; STAGING SYSTEM; PORTAL-VEIN; THERAPY;
D O I
10.1002/bjs.10776
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: Although some retrospective studies have suggested the value of adjuvant therapy, no recommended standard exists in bile duct cancer. The aim of this study was to test the hypothesis that adjuvant gemcitabine chemotherapy would improve survival probability in resected bile duct cancer. Methods: This was a randomized phase III trial. Patients with resected bile duct cancer were assigned randomly to gemcitabine and observation groups, which were balanced with respect to lymph node status, residual tumour status and tumour location. Gemcitabine was given intravenously at a dose of 1000 mg/m(2), administered on days 1, 8 and 15 every 4 weeks for six cycles. The primary endpoint was overall survival, and secondary endpoints were relapse-free survival, subgroup analysis and toxicity. Results: Some 225 patients were included (117 gemcitabine, 108 observation). Baseline characteristics were well balanced between the gemcitabine and observation groups. There were no significant differences in overall survival (median 62.3 versus 63.8 months respectively; hazard ratio 1.01, 95 per cent c.i. 0.70 to 1.45; P=0.964) and relapse-free survival (median 36.0 versus 39.9 months; hazard ratio 0.93, 0.66 to 1.32; P=0.693). There were no survival differences between the two groups in subsets stratified by lymph node status and margin status. Although haematological toxicity occurred frequently in the gemcitabine group, most toxicities were transient, and grade 3/4 non-haematological toxicity was rare. Conclusion: The survival probability in patients with resected bile duct cancer was not significantly different between the gemcitabine adjuvant chemotherapy group and the observation group.
引用
收藏
页码:192 / 202
页数:11
相关论文
共 37 条
[1]  
[Anonymous], 2006, COMMON TERMINOLOGY C
[2]  
Bridgewater JA, 2011, J CLIN ONCOL, V29
[3]   Hepatectomy with portal vein resection for hilar cholangiocarcinoma - Audit of 52 consecutive cases [J].
Ebata, T ;
Nagino, M ;
Kamiya, J ;
Uesaka, K ;
Nagasaka, T ;
Nimura, Y .
ANNALS OF SURGERY, 2003, 238 (05) :720-727
[4]   Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas [J].
Ebata, T. ;
Kosuge, T. ;
Hirano, S. ;
Unno, M. ;
Yamamoto, M. ;
Miyazaki, M. ;
Kokudo, N. ;
Miyagawa, S. ;
Takada, T. ;
Nagino, M. .
BRITISH JOURNAL OF SURGERY, 2014, 101 (02) :79-88
[5]   Hepatopancreatoduodenectomy for Cholangiocarcinoma A Single-Center Review of 85 Consecutive Patients [J].
Ebata, Tomoki ;
Yokoyama, Yukihiro ;
Igami, Tsuyoshi ;
Sugawara, Gen ;
Takahashi, Yu ;
Nimura, Yuji ;
Nagino, Masato .
ANNALS OF SURGERY, 2012, 256 (02) :297-305
[6]   Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. [J].
Edeline, Julien ;
Bonnetain, Franck ;
Phelip, Jean Marc ;
Watelet, Jerome ;
Hammel, Pascal ;
Joly, Jean-Paul ;
Ben Abdelghani, Meher ;
Rosmorduc, Olivier ;
Bouhier-Leporrier, Karine ;
Jouve, Jean-Louis ;
Faroux, Roger ;
Meyer, Veronique Guerin ;
Assenat, Eric ;
Seitz, Jean Francois ;
Malka, David ;
Louvet, Christophe ;
Bertaut, Aurelie ;
Juzyna, Beata ;
Stanbury, Trevor ;
Boucher, Eveline .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (04)
[7]   Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101) [J].
Fujiwara, Yutaka ;
Kobayashi, Shogo ;
Nagano, Hiroaki ;
Kanai, Masashi ;
Hatano, Etsuo ;
Toyoda, Masanori ;
Ajiki, Tetsuo ;
Takashima, Yuki ;
Yoshimura, Kenichi ;
Hamada, Akinobu ;
Minami, Hironobu ;
Ioka, Tatsuya .
PLOS ONE, 2015, 10 (12)
[8]   Neither Neoadjuvant nor Adjuvant Therapy Increases Survival After Biliary Tract Cancer Resection with Wide Negative Margins [J].
Glazer, Evan S. ;
Liu, Ping ;
Abdalla, Eddie K. ;
Vauthey, Jean-Nicolas ;
Curley, Steven A. .
JOURNAL OF GASTROINTESTINAL SURGERY, 2012, 16 (09) :1666-1671
[9]   Is There a Role for Adjuvant Therapy in RO Resected Gallbladder Cancer?: A Propensity Score-Matched Analysis [J].
Go, Se-Il ;
Kim, Young Saing ;
Hwang, In Gyu ;
Kim, Eun Young ;
Oh, Sung Yong ;
Ji, Jun Ho ;
Song, Haa-Na ;
Park, Se Hoon ;
Park, Joon Oh ;
Kang, Jung Hun .
CANCER RESEARCH AND TREATMENT, 2016, 48 (04) :1274-1285
[10]   Adjuvant Therapy in the Treatment of Biliary Tract Cancer: A Systematic Review and Meta-Analysis [J].
Horgan, Anne M. ;
Amir, Eitan ;
Walter, Thomas ;
Knox, Jennifer J. .
JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (16) :1934-1940