Abstract
Purpose
To evaluate the feasibility of S-1 plus cisplatin as adjuvant chemotherapy for stage III gastric cancer after curative resection.
Methods
Japanese patients with stage III gastric cancer who underwent gastrectomy with D2 lymph node resection were enrolled. Treatment consisted of 3 cycles of S-1 (80 mg/m2/day, b.i.d.) for 21 days followed by a 14-day rest, and cisplatin (60 mg/m2 iv) on day 8. After that, S-1 monotherapy was given on days 1–28 every 6 weeks until 1-year postsurgery. After protocol amendment, the first chemotherapy cycle consisted of S-1 monotherapy; cisplatin was added to cycles 2, 3, and 4, followed by S-1 monotherapy up to 1-year postsurgery. The primary endpoint was the completion rate of three cycles of S-1 plus cisplatin.
Results
A total of 63 enrolled patients have been evaluated. Grade 3/4 toxicities included neutropenia (40%), anorexia (28%), and febrile neutropenia (4%) before protocol amendment (n = 25), and neutropenia (37%), anorexia (8%), and febrile neutropenia (3%) after amendment implementation (n = 38). Excluding ineligible cases, treatment completion rates were 57% (12/21) before and 81% (30/37) after the protocol amendment.
Conclusions
The amended S-1 plus cisplatin is more feasible than the original protocol because of early dose reduction of S-1 prior to cisplatin addition and greater recovery time from surgery prior to cisplatin. This treatment should be considered as a feasible experimental arm for the next postoperative adjuvant phase III trial.
Similar content being viewed by others
References
http://www.who.int/mediacentre/factsheets/fs297/en/index.html
Cirera L, Balil A, Batise-Alentorn E et al (1999) Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. J Clin Oncol 17:3810–3815
Nakajima T, Nashimoto A, Kitamura M et al (1999) Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Lancet 354:273–277
Neri B, Cini G, Andreoli F et al (2001) Randomized trial of adjuvant chemotherapy versus control after curative resection for gastric cancer: 5-year follow-up. Br J Cancer 84:878–880
Bajetta E, Buzzoni R, Mariani L et al (2002) Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian trials in medical oncology (ITMO) group. Ann Oncol 13:299–307
Nashimoto A, Nakajima T, Furukawa H et al (2003) Randomized trial of adjuvant chemotherapy with mitomycin, fluorouracil, and cytosine arabinoside followed by oral fluorouracil in serosa-negative gastric cancer: Japan clinical oncology group 9206-1. J Clin Oncol 21:2282–2287
Chipponi J, Huguier M, Pezet D et al (2004) Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer. Am J Surg 187:440–445
Popiela T, Kulig J, Czupryna A et al (2004) Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer. Gastric Cancer 7:240–245
Bouche O, Ychou M, Burtin P et al (2005) Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol 16:1488–1497
Nitti D, Wils J, Santos GD et al (2006) Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI group and the ICCG. Ann Oncol 17:262–269
De Vita F, Giuliani F, Orditura M et al (2007) Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study). Ann Oncol 18:1354–1358
Nakajima T, Kinoshita T, Nashimoto A et al (2007) Randomized controlled trial of adjuvant uracil-tegafur versus surgery alone for serosa-negative, locally advanced gastric cancer. Br J Surg 94:1468–1476
GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group (2010) Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA 303:1729–1737
Shirasaka T, Shimamoto Y, Ohshimo H et al (1996) 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
Sakuramoto S, Sasako M, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820
Koizumi W, Narahara H, Hara T et al (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221
Ajani JA, Rodriguez W, Bodoky G et al (2010) Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol 28(9):1547–1553
Japanese Gastric Cancer Association (1998) Japanese classification of gastric carcinoma, 2nd english ed. Gastric Cancer 1:10–24
Cascinu S, Labianca R, Barone C et al (2007) Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Inst 99:601–607
Ellenberg SS, Sun W (2007) Adjuvant therapy for gastric cancer: how negative results can help patients. J Natl Cancer Inst 99:580–582
Tsuruoka Y, Kamano T, Kitajima M et al (2006) Effect of gastrectomy on the pharmacokinetics of 5-fluorouracil and gimeracil after oral administration of S-1. Anticancer Drugs 17:393–399
Kochi M, Fujii M, Kanamori N et al (2007) Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients. Cancer Chemother Pharmacol 60:693–701
Kim WY, Nakata B, Hirakawa K (2007) Alternative pharmacokinetics of S-1 components, 5-fluorouracil, dihydrofluorouracil and alpha-fluoro-beta-alanine after oral administration of S-1 following total gastrectomy. Cancer Sci 98:1604–1608
Kinura Y, Tamura S, Fujitani K et al (2010) Phase II study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy(OGSG0604). In: 2010 Gastrointestinal cancers symposium abstr #100
Acknowledgments
We thank Mr. Yushi Nagai and Ms. Michiyo Tada for help in collecting and organizing the database. We received no financial support.
Conflicts of interest
T. Sano has received lecture fees from Taiho Pharmaceutial (Tokyo, Japan). All other authors declared no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takahari, D., Hamaguchi, T., Yoshimura, K. et al. Feasibility study of adjuvant chemotherapy with S-1 plus cisplatin for gastric cancer. Cancer Chemother Pharmacol 67, 1423–1428 (2011). https://doi.org/10.1007/s00280-010-1432-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-010-1432-8