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Published in: World Journal of Surgery 11/2014

01-11-2014 | Original Scientific Report

S-1 vs. Gemcitabine as an Adjuvant Therapy after Surgical Resection for Ductal Adenocarcinoma of the Pancreas

Authors: Takehiro Okabayashi, Yasuo Shima, Jun Iwata, Sojiro Morita, Tatsuaki Sumiyoshi, Akihito Kozuki, Teppei Tokumaru, Tatsuo Iiyama, Takuhiro Kosaki, Michiya Kobayashi, Kazuhiro Hanazaki

Published in: World Journal of Surgery | Issue 11/2014

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Abstract

Background

Pancreatectomy with regional lymphadenectomy remains the only curative treatment option for pancreatic cancer. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer.

Objective

Our objective was to retrospectively evaluate whether postoperative adjuvant chemotherapy using S-1 is clinically beneficial in managing resectable pancreatic cancer.

Methods

Patients were divided into three groups: those undergoing surgery alone, those receiving gemcitabine infusion, and those receiving S-1 orally.

Results

Of 189 studied patients, the median overall survival was 15.0 months after surgery alone, 33.0 months in the gemcitabine group, and 45.0 months in patients receiving S-1. A multivariate analysis identified regional lymph node metastasis, positive surgical margins, and absence of adjuvant chemotherapy as independent negative prognostic factors. S-1 was not inferior to gemcitabine in terms of survival outcomes and showed a favorable hazard ratio compared with gemcitabine in the subsets of patients with positive vascular invasion.

Conclusions

There was no difference between adjuvant chemotherapy with S-1 and gemcitabine in overall survival for patients with curative pancreatic cancer. Our results suggested that S-1 can be used as a second agent to gemcitabine after surgical resection for ordinary adenocarcinoma of the pancreas.
Literature
1.
go back to reference Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277PubMedCrossRef Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277PubMedCrossRef
2.
go back to reference Neoptolemos JP, Stocken DD, Friess H et al (2004) European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210PubMedCrossRef Neoptolemos JP, Stocken DD, Friess H et al (2004) European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210PubMedCrossRef
3.
go back to reference Choti MA (2004) Adjuvant therapy for pancreatic cancer–the debate continues. N Engl J Med 350:1249–1251PubMedCrossRef Choti MA (2004) Adjuvant therapy for pancreatic cancer–the debate continues. N Engl J Med 350:1249–1251PubMedCrossRef
4.
go back to reference Michalski CW, Kleeff J, Wente MN et al (2007) Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg 94:265–273PubMedCrossRef Michalski CW, Kleeff J, Wente MN et al (2007) Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg 94:265–273PubMedCrossRef
5.
go back to reference Konstantinidis IT, Warshaw AL, Allen JN et al (2013) Pancreatic ductal adenocarcinoma: is there a survival difference for r1 resections versus locally advanced unresectable tumors? what is a “true” r0 resection? Ann Surg 257:731–736PubMedCrossRef Konstantinidis IT, Warshaw AL, Allen JN et al (2013) Pancreatic ductal adenocarcinoma: is there a survival difference for r1 resections versus locally advanced unresectable tumors? what is a “true” r0 resection? Ann Surg 257:731–736PubMedCrossRef
6.
go back to reference Mollberg N, Rahbari NN, Koch M et al (2011) Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg 254:882–893PubMedCrossRef Mollberg N, Rahbari NN, Koch M et al (2011) Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg 254:882–893PubMedCrossRef
8.
go back to reference Birkmeyer JD, Stukel TA, Siewers AE et al (2003) Surgeon volume and operative mortality in the United States. N Engl J Med 349:2117–2127PubMedCrossRef Birkmeyer JD, Stukel TA, Siewers AE et al (2003) Surgeon volume and operative mortality in the United States. N Engl J Med 349:2117–2127PubMedCrossRef
9.
go back to reference Yeo CJ, Cameron JL, Lillemoe KD et al (2002) 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 236:355–366PubMedCrossRefPubMedCentral Yeo CJ, Cameron JL, Lillemoe KD et al (2002) 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 236:355–366PubMedCrossRefPubMedCentral
10.
go back to reference Neoptolemos JP, Stocken DD, Bassi C et al (2010) European study group for pancreatic cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081PubMedCrossRef Neoptolemos JP, Stocken DD, Bassi C et al (2010) European study group for pancreatic cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081PubMedCrossRef
11.
go back to reference Regine WF, Winter KA, Abrams RA et al (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299:1019–1026PubMedCrossRef Regine WF, Winter KA, Abrams RA et al (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299:1019–1026PubMedCrossRef
12.
go back to reference Berger AC, Garcia M Jr, Hoffman JP et al (2008) Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 26:5918–5922PubMedCrossRefPubMedCentral Berger AC, Garcia M Jr, Hoffman JP et al (2008) Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 26:5918–5922PubMedCrossRefPubMedCentral
13.
go back to reference Conroy T, Desseigne F, Ychou M et al (2011) Groupe tumeurs digestives of unicancer; prodige intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825PubMedCrossRef Conroy T, Desseigne F, Ychou M et al (2011) Groupe tumeurs digestives of unicancer; prodige intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825PubMedCrossRef
14.
go back to reference Ueno H, Okusaka T, Ikeda M et al (2005) A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer. Oncology 69:421–427PubMedCrossRef Ueno H, Okusaka T, Ikeda M et al (2005) A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer. Oncology 69:421–427PubMedCrossRef
15.
go back to reference Okusaka T, Funakoshi A, Furuse J et al (2008) A late phase II study of S-1 for metastatic pancreatic cancer. Cancer Chemother Pharmacol 61:615–621PubMedCrossRef Okusaka T, Funakoshi A, Furuse J et al (2008) A late phase II study of S-1 for metastatic pancreatic cancer. Cancer Chemother Pharmacol 61:615–621PubMedCrossRef
16.
go back to reference Ueno H, Ioka T, Ikeda M et al (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 31:1640–1648PubMedCrossRef Ueno H, Ioka T, Ikeda M et al (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 31:1640–1648PubMedCrossRef
17.
go back to reference Cascinu S, Jelic S (2009) ESMO guidelines. Working group pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 20(Suppl 4):37–40PubMed Cascinu S, Jelic S (2009) ESMO guidelines. Working group pancreatic cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 20(Suppl 4):37–40PubMed
18.
go back to reference Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457CrossRef Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457CrossRef
19.
go back to reference Cox DR (1972) Regression models and life tables. J R Stat Soc 187:34B Cox DR (1972) Regression models and life tables. J R Stat Soc 187:34B
20.
go back to reference Uesaka K, Fukutomi A, Boku N et al (2012) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study). J Clin Oncol 30 (Suppl 34; abstract 145) Uesaka K, Fukutomi A, Boku N et al (2012) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study). J Clin Oncol 30 (Suppl 34; abstract 145)
21.
go back to reference Chaulagain CP, Ng J, Goodman MD et al (2013) Adjuvant therapy of pancreatic cancer. JOP 14:119–122PubMed Chaulagain CP, Ng J, Goodman MD et al (2013) Adjuvant therapy of pancreatic cancer. JOP 14:119–122PubMed
22.
go back to reference Haller DG, Cassidy J, Clarke SJ et al (2008) Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol 26:2118–2123PubMedCrossRef Haller DG, Cassidy J, Clarke SJ et al (2008) Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol 26:2118–2123PubMedCrossRef
23.
go back to reference Chuah B, Goh BC, Lee SC et al (2011) Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients. Cancer Sci 102:478–483PubMedCrossRef Chuah B, Goh BC, Lee SC et al (2011) Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients. Cancer Sci 102:478–483PubMedCrossRef
24.
go back to reference Murakami Y, Uemura K, Sudo T et al (2013) Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection. Cancer Chemother Pharmacol 71(2):419–429PubMedCrossRef Murakami Y, Uemura K, Sudo T et al (2013) Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection. Cancer Chemother Pharmacol 71(2):419–429PubMedCrossRef
25.
go back to reference Murakami Y, Uemura K, Sudo T et al (2012) Long-term results of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic carcinoma. J Surg Oncol 106:174–180PubMedCrossRef Murakami Y, Uemura K, Sudo T et al (2012) Long-term results of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic carcinoma. J Surg Oncol 106:174–180PubMedCrossRef
26.
go back to reference Neoptolemos JP, Cunningham D, Friess H et al (2003) Adjuvant therapy in pancreatic cancer: historical and current perspectives. Ann Oncol 14:675–692PubMedCrossRef Neoptolemos JP, Cunningham D, Friess H et al (2003) Adjuvant therapy in pancreatic cancer: historical and current perspectives. Ann Oncol 14:675–692PubMedCrossRef
Metadata
Title
S-1 vs. Gemcitabine as an Adjuvant Therapy after Surgical Resection for Ductal Adenocarcinoma of the Pancreas
Authors
Takehiro Okabayashi
Yasuo Shima
Jun Iwata
Sojiro Morita
Tatsuaki Sumiyoshi
Akihito Kozuki
Teppei Tokumaru
Tatsuo Iiyama
Takuhiro Kosaki
Michiya Kobayashi
Kazuhiro Hanazaki
Publication date
01-11-2014
Publisher
Springer US
Published in
World Journal of Surgery / Issue 11/2014
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-014-2703-z

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