Abstract
Background
The factors which affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated in pancreatic cancer. The objective of this retrospective study was to clarify the risk factors for the discontinuation of S-1 adjuvant chemotherapy after 6 months of treatment.
Methods
The study included patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II or III disease, had a serum creatinine level ≤1.2 mg/dl and received adjuvant S-1 between June 2007 and March 2014.
Results
Forty patients were eligible for the present study. A comparison of the 6-month continuation stratified by each clinical factor using the log-rank test revealed a significant difference in the creatinine clearance (CCr) between the patients who continued and discontinued the treatment. A CCr of 60 ml/min was regarded as a critical point. The uni- and multivariate Cox’s proportional hazard analyses demonstrated that the CCr was the only significant independent predictive factor. The 6-month continuation rate was 70.8 % in the patients with a CCr ≥60 ml/min and was 25.0 % in patients with a CCr <60 ml/min (P = 0.008). The patients with a CCr <60 ml/min developed adverse events more frequently and earlier than those with a CCr ≥60 ml/min.
Conclusions
A CCr < 60 ml/min was a significant risk factor for the 6-month discontinuation of S-1 adjuvant chemotherapy in pancreatic cancer patients, even though the renal function was judged to be normal based on the serum creatinine level. Careful attention is therefore required to improve the S-1 continuation in patients with a CCr < 60 ml/min.
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References
International Agency for Research on Cancer, World Health Organization. Globocan 2008. World Health Organization Web site. http://globocan.iarc.fr/. Accessed 15 July 2010
Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300
Uesaka K, Fukutomi A, Boku N, Kanemoto H, Konishi M, Matsumoto I et al (2013) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for resected pancreatic cancer patients (JASPAC-01 study). J Clin Oncol 31;suppl 4: abstr 145
Bonadonna G, Valagussa P (1981) Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl J Med 304:101–105
Sobin LH, Wittekind CH (eds) (2002) TNM classification of malignant tumors, 6th edn. Wiley, New York
Maeda A, Boku N, Fukutomi A, Kondo S, Kinoshita T, Nagino M et al (2008) Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 in patients with resected pancreatic cancer: Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC-01). Jpn J Clin Oncol 38:227–229
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41
Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K 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
Tatsumi K, Fukushima M, Shirasaka T, Fujii S (1987) Inhibitory effects of pyrimidine, barbituric acid and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res 78:748–755
Hirata K, Horikoshi N, Aiba K, Okazaki M, Denno R, Sasaki K et al (1999) Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug. Clin Cancer Res 5:2000–2005
Aoyama T, Yoshikawa T, Hayashi T, Kuwabara H, Mikayama Y, Ogata T et al (2013) Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for gastric cancer. Gastric Cancer 16:133–139
Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M (2008) Safety evaluation of oral fluoropyrimidine S-1 for short- and long-term delivery in advanced gastric cancer: analysis of 3,758 patients. Cancer Chemother Pharmacol 61:335–343
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Toru Aoyama and Yusuke Katayama have contributed equally to this article.
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Aoyama, T., Katayama, Y., Murakawa, M. et al. Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for resected pancreatic cancer. Cancer Chemother Pharmacol 74, 1235–1240 (2014). https://doi.org/10.1007/s00280-014-2601-y
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DOI: https://doi.org/10.1007/s00280-014-2601-y