Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for resectable pancreatic cancer

Tajima,Hidehiro; Ohta,Tetsuo; Kitagawa,Hirohisa; Okamoto,Koichi; Sakai,Seisho; Makino,Isamu; Kinoshita,Jun; Furukawa,Hiroyuki; Nakamura,Keishi; Hayashi,Hironori; Oyama,Katsunobu; Inokuchi,Masafumi; Nakagawara,Hisatoshi; Fujita,Hideto; Takamura,Hiroyuki; Ninomiya,Itasu; Fushida,Sachio; Tani,Takashi; Fujimura,Takashi; Ikeda,Hiroko; Kitamura,Seiko

doi:10.3892/etm.2012.482

Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for resectable pancreatic cancer

Authors:
- Hidehiro Tajima
- Tetsuo Ohta
- Hirohisa Kitagawa
- Koichi Okamoto
- Seisho Sakai
- Isamu Makino
- Jun Kinoshita
- Hiroyuki Furukawa
- Keishi Nakamura
- Hironori Hayashi
- Katsunobu Oyama
- Masafumi Inokuchi
- Hisatoshi Nakagawara
- Hideto Fujita
- Hiroyuki Takamura
- Itasu Ninomiya
- Sachio Fushida
- Takashi Tani
- Takashi Fujimura
- Hiroko Ikeda
- Seiko Kitamura
View Affiliations

Affiliations: Department of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, Kanazawa, Japan, Division of Pathology, Kanazawa University Hospital, Kanazawa, Japan
Published online on: February 13, 2012 https://doi.org/10.3892/etm.2012.482
Pages: 787-792

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Results of surgery alone for pancreatic cancer are disappointing. We retrospectively evaluated the efficacy and tolerability of neoadjuvant chemotherapy (NAC) with gemcitabine and oral S-1 in patients with potentially resectable pancreatic cancer. A total of 34 patients with pancreatic ductal adenocarcinoma, radiologically diagnosed preoperatively as having potentially resectable tumors, underwent pancreatic resection with lymphadenectomy at Kanazawa University Hospital. NAC was administered to 13 patients (NAC group). The remaining 21 patients were surgically treated without preoperative chemotherapy (control group). Surgical results were compared between these two groups, with follow-up for at least 24 months. No statistically significant differences were found in the clinicopathological background data (tumor location, age, gender, lymph node metastases, tumor stage and tumor size) between the NAC and control groups. Following preoperative chemotherapy, no patients were judged to be unable to undergo laparotomy, i.e., neither distant metastasis nor tumor progression was observed. Radiologically, all 13 NAC group patients had stable disease, whereas, histopathologically, all tumor specimens showed evidence of tumor cells. The treatment effect was judged by Evans grading to be grade IIa in 11 patients and grade IIb in 2 patients. Toxicity was evaluated in 11 patients. Grade III side effects were regarded as hematological toxicity, i.e., leucopenia (7.7%) and thrombocytopenia (15.4%). Moreover, the incidence of perioperative complications did not differ significantly between the NAC and control groups. The one- and three-year overall survival rates of the NAC group with pancreatic head cancer were 88.9 and 55.6%, respectively, superior to 88.9 and 29.6% in the control group (p=0.055). Therefore, NAC with gemcitabine and S-1 is well tolerated and potentially effective against pancreatic head cancer. A phase I study of NAC with gemcitabine and S-1 is under way in patients with resectable pancreatic cancer.

View Figures

View References

1.	Ministry of Health, Labour and Welfare: The Dynamic Statistics of the Population in 2005. http://www.mhlw.go.jp/toukei/saikin/hw/jinkou/kakutei05/hyo7/htmluri (11 June 2009, data last accepted).
2.	Ishii H, Furuse J, Boku N, et al: Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506. Jpn J Clin Oncol. View Article : Google Scholar : 2010. View Article : Google Scholar : PubMed/NCBI
3.	Nagakawa T, Kurachi M, Konishi K, et al: Translateral retroperitoneal approach in radical surgery for pancreatic carcinoma. Jpn J Surg. 12:229–233. 1982. View Article : Google Scholar : PubMed/NCBI
4.	Nagakawa T, Nagamori M, Futakami F, et al: Result of extensive surgery for pancreatic carcinoma. Cancer. 77:640–645. 1996. View Article : Google Scholar : PubMed/NCBI
5.	Miwa K, Ohta T, Shimizu K, et al: Augmented regional pancreatoduodenectomy for pancreas head cancer: combined resection of pancreas head and superior mesenteric artery and vein. In: American College of Surgeons 90th Annual Clinical Congress; Chicago. Isis 190. 2004
6.	Evans DB, Abbruzzese JL and Willett CG: Cancer of the pancreas. Cancer: Principles and Practice of Oncology. 6th edition. De Vita Hellman S and Rosenberg SA: Lippincott, Williams and Wilkins; Philadelphia: pp. 1126–1161. 2001
7.	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. View Article : Google Scholar
8.	Klinlenbijl 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. View Article : Google Scholar
9.	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.PubMed/NCBI
10.	Yeo CJ, Abrams RA, Grochow LB, et al: Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg. 225:621–633. 1997. View Article : Google Scholar
11.	Shirasaka T, Shimamoto Y, Ohshimo H, et al: Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs. 7:548–557. 1996. View Article : Google Scholar : PubMed/NCBI
12.	Tatsumi K, Fukushima M, Shirasaki T and Fujii S: Inhibitory effects of pyrimidine, barbituric acid and pyrimidine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res. 78:748–755. 1987.PubMed/NCBI
13.	Takechi T, Fujioka A, Matssushima E, et al: Enhancement of the antitumor activity of 5-fluorouracil (5-FU) by inhibiting dihydropyrimidine dehydrogenase activity (DPD) using 5-chloro-2,4-dihydroxypyridine (CDHP) in human tumor cells. Eur J Cancer. 38:1271–1277. 2002. View Article : Google Scholar
14.	Peters GJ, van Groeningen CJ, Laurensse EJ and Pinedo HM: A compression of 5-fluorouracil metabolism in human colorectal cancer and colon mucosa. Cancer. 68:1903–1909. 1991. View Article : Google Scholar : PubMed/NCBI
15.	Takechi T, Nakano K, Uchida J, et al: Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother Pharmacol. 39:205–211. 1997. View Article : Google Scholar : PubMed/NCBI
16.	Nakamura K, Yamaguchi T, Ishihara T, et al: Phase I trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer. Br J Cancer. 92:2134–2139. 2005. View Article : Google Scholar : PubMed/NCBI
17.	Ueno H, Okusaka T, Ikeda M, et al: A phase I study of combination chemotherapy with gemcitabine and oral S-1 for advanced pancreatic cancer. Oncology. 69:421–427. 2005. View Article : Google Scholar : PubMed/NCBI
18.	Nakamura K, Yamaguchi T, Ishihara T, et al: Phase II trial of oral S-1 combined with gemcitabine in metastatic pancreatic cancer. Br J Cancer. 1–5. 2006.PubMed/NCBI
19.	Vento P, Mustonen H, Joensuu T, et al: Impact of preoperative chemoradiotherapy on survival in patients with resectable pancreatic cancer. World J Gastroenterol. 21:2945–2951. 2007.PubMed/NCBI
20.	Palmer DH, Stocken DD, Hewitt H, et al: A randomized phase 2 trial of neo-adjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol. 14:2088–2096. 2007. View Article : Google Scholar
21.	Sato N, Kurashima K, Nagai H, et al: The effect of adjuvant and neoadjuvant chemo (radio) therapy on survival in 1,679 resected pancreatic carcinoma cases in Japan: report of the national survey in the 34th annual meeting of Japanese Society of Pancreatic Surgery. J Hepatobiliary Pancreat Surg. 16:485–492. 2009. View Article : Google Scholar
22.	Satoi S, Yanagimoto H, Toyokawa H, et al: Surgical result after preoperative chemoradiation therapy for patients with pancreatic cancer. Pancreas. 38:282–288. 2008. View Article : Google Scholar : PubMed/NCBI
23.	Rauchwerger DR, Firby PS, Hedley DW and Moore MJ: Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res. 60:6075–6079. 2000.PubMed/NCBI
24.	Makino I, Kitagawa H, Ohta T, et al: Nerve plexus invasion in pancreatic cancer. Spread patterns on histopathologic and embryological analysis. Pancreas. 37:358–365. 2008. View Article : Google Scholar : PubMed/NCBI
25.	Evans DB, Rich TA, Byrd DR, et al: Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 127:1335–1339. 1992. View Article : Google Scholar : PubMed/NCBI
26.	Esposito I, Kleeff J, Bergmann F, et al: Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 15:1651–1660. 2008. View Article : Google Scholar : PubMed/NCBI
27.	Nakahira S, Nakamori S, Tsujie M, et al: Pretreatment with S-1, an oral derivative of 5-fluorouracil, enhances gemcitabine effect in pancreatic cancer xenografts. Anticancer Res. 28:179–186. 2008.PubMed/NCBI
28.	Takai S, Satoi S, Yanagimoto H, et al: Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer. Pancreas. 36:26–32. 2008. View Article : Google Scholar : PubMed/NCBI
29.	Golcher H, Brunner T, Grabenbauer G, et al: Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy. EJSO. 34:756–764. 2008. View Article : Google Scholar : PubMed/NCBI
30.	Van Laethem JL, Hammel P, Mornex F, et al: Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: A randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. J Clin Oncol. 28:4450–4456. 2010.