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. 2001 Sep;85(7):939–943. doi: 10.1054/bjoc.2001.2031

Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer

M Kawahara 1, K Furuse 1, Y Segawa 2, K Yoshimori 3, K Matsui 4, S Kudoh 5, K Hasegawa 6, H Niitani 7; S-1 Cooperative Study Group (Lung Cancer Working Group)7
PMCID: PMC2375091  PMID: 11592762

Abstract

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m−2day−1: BSA < 1.25 m2, 40 mg b.i.d.; BSA≥1.25 but <1.5 m2; 50 mg b.i.d., and BSA≥1.5 m2: 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3–34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1–13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7–14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active single agent against NSCLC. Further study of S-1 with other active agents is warranted. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

Keywords: NSCLC, tegafur, CDHP, S-1

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Selected References

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  1. Ansfield F. J., Kallas G. J., Singson J. P. Phase I-II studies of oral tegafur (ftorafur). J Clin Oncol. 1983 Feb;1(2):107–110. doi: 10.1200/JCO.1983.1.2.107. [DOI] [PubMed] [Google Scholar]
  2. Blum J. L., Jones S. E., Buzdar A. U., LoRusso P. M., Kuter I., Vogel C., Osterwalder B., Burger H. U., Brown C. S., Griffin T. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol. 1999 Feb;17(2):485–493. doi: 10.1200/JCO.1999.17.2.485. [DOI] [PubMed] [Google Scholar]
  3. Giller S. A., Zhuk R. A., Lidak M. Iu. Analogi pirimidinnukleozidov. I. N1-(alpha-furanidil'nye)-proizvodnye prirodnykh pirimidinovykh osvanii i ikh antimetabolitov. Dokl Akad Nauk SSSR. 1967 Sep 11;176(2):332–335. [PubMed] [Google Scholar]
  4. Hara Y. [5'-Deoxy-5-fluorouridine enzymatic activation from the masked compound to 5-fluorouracil in human malignant tissues]. Gan To Kagaku Ryoho. 1984 Oct;11(10):2133–2143. [PubMed] [Google Scholar]
  5. Harris B. E., Song R., Soong S. J., Diasio R. B. Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion. Cancer Res. 1990 Jan 1;50(1):197–201. [PubMed] [Google Scholar]
  6. Heggie G. D., Sommadossi J. P., Cross D. S., Huster W. J., Diasio R. B. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 1987 Apr 15;47(8):2203–2206. [PubMed] [Google Scholar]
  7. Hirata K., Horikoshi N., Aiba K., Okazaki M., Denno R., Sasaki K., Nakano Y., Ishizuka H., Yamada Y., Uno S. Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug. Clin Cancer Res. 1999 Aug;5(8):2000–2005. [PubMed] [Google Scholar]
  8. Ichinose Y., Takanashi N., Yano T., Asoh H., Yokoyama H., Tayama K., Hara N., Ohta M. A phase II trial of oral tegafur and uracil plus cisplatin in patients with inoperable nonsmall cell lung cancer. Cancer. 1995 Jun 1;75(11):2677–2680. doi: 10.1002/1097-0142(19950601)75:11<2677::aid-cncr2820751106>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  9. Ikenaka K., Shirasaka T., Kitano S., Fujii S. Effect of uracil on metabolism of 5-fluorouracil in vitro. Gan. 1979 Jun;70(3):353–359. [PubMed] [Google Scholar]
  10. Keicho N., Saijo N., Shinkai T., Eguchi K., Sasaki Y., Tamura T., Sakurai M., Sano T., Hoshi A. Phase II study of UFT in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 1986 Jun;16(2):143–146. doi: 10.1093/oxfordjournals.jjco.a039130. [DOI] [PubMed] [Google Scholar]
  11. Lokich J. J., Ahlgren J. D., Gullo J. J., Philips J. A., Fryer J. G. A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study. J Clin Oncol. 1989 Apr;7(4):425–432. doi: 10.1200/JCO.1989.7.4.425. [DOI] [PubMed] [Google Scholar]
  12. Moynihan T., Hansen R., Anderson T., Quebbeman E., Beatty P., Ausman R., Ritch P., Chitambar C., Vukelich M. Continuous 5-fluorouracil infusion in advanced gastric carcinoma. Am J Clin Oncol. 1988 Aug;11(4):461–464. doi: 10.1097/00000421-198808000-00010. [DOI] [PubMed] [Google Scholar]
  13. Nakai Y., Furuse K., Ohta M., Yamaguchi Y., Fujii M., Asakawa M., Fukuoka M., Yoshida K., Niitani H. Efficacy of a new 5-fluorouracil derivative, BOF-A2, in advanced non-small cell lung cancer. A multi-center phase II study. Acta Oncol. 1994;33(5):523–526. doi: 10.3109/02841869409083929. [DOI] [PubMed] [Google Scholar]
  14. Niitani H., Kimura K., Saito T., Nakao I., Abe O., Urushizaki I., Ohta K., Yoshida Y., Kimura T., Kurihara M. [Phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with malignant cancer--a multi-institutional cooperative study]. Gan To Kagaku Ryoho. 1985 Oct;12(10):2044–2051. [PubMed] [Google Scholar]
  15. Ota K., Taguchi T., Kimura K. Report on nationwide pooled data and cohort investigation in UFT phase II study. Cancer Chemother Pharmacol. 1988;22(4):333–338. [PubMed] [Google Scholar]
  16. Richards F., 2nd, Perry D. J., Goutsou M., Modeas C., Muchmore E., Rege V., Chahinian A. P., Hirsh V., Poiesz B., Green M. R. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin or 5-FU, cisplatin, and vinblastine for advanced non-small cell lung cancer. A randomized phase II study of the cancer and leukemia group B. Cancer. 1991 Jun 15;67(12):2974–2979. doi: 10.1002/1097-0142(19910615)67:12<2974::aid-cncr2820671206>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  17. Seifert P., Baker L. H., Reed M. L., Vaitkevicius V. K. Comparison of continuously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma. Cancer. 1975 Jul;36(1):123–128. doi: 10.1002/1097-0142(197507)36:1<123::aid-cncr2820360108>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  18. Shirasaka T., Nakano K., Takechi T., Satake H., Uchida J., Fujioka A., Saito H., Okabe H., Oyama K., Takeda S. Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats. Cancer Res. 1996 Jun 1;56(11):2602–2606. [PubMed] [Google Scholar]
  19. Shirasaka T., Shimamato Y., Ohshimo H., Yamaguchi M., Kato T., Yonekura K., Fukushima M. 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. 1996 Jul;7(5):548–557. doi: 10.1097/00001813-199607000-00010. [DOI] [PubMed] [Google Scholar]
  20. Shirasaka T., Shimamoto Y., Fukushima M. Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats. Cancer Res. 1993 Sep 1;53(17):4004–4009. [PubMed] [Google Scholar]
  21. Taguchi T., Inuyama Y., Kanamaru R., Hasegawa K., Akazawa S., Niitani H., Furue H., Kurihara M., Ota K., Suga S. [Phase I study of S-1. S-1 Study Group]. Gan To Kagaku Ryoho. 1997 Dec;24(15):2253–2264. [PubMed] [Google Scholar]
  22. Tatsumi K., Fukushima M., Shirasaka T., Fujii S. Inhibitory effects of pyrimidine, barbituric acid and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res. 1987 Jul;78(7):748–755. [PubMed] [Google Scholar]
  23. Unemi N., Harima K., Daidai Y., Fujihara H., Fujii S. [Experimental studies on antineoplastic action of N 1 -(2'-tetrahydrofuryl)-5-fluorouracil (FT-207)--effect on experimental tumors]. Gan No Rinsho. 1971 Oct;17(10):731–742. [PubMed] [Google Scholar]
  24. Van Cutsem E., Findlay M., Osterwalder B., Kocha W., Dalley D., Pazdur R., Cassidy J., Dirix L., Twelves C., Allman D. Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study. J Clin Oncol. 2000 Mar;18(6):1337–1345. doi: 10.1200/JCO.2000.18.6.1337. [DOI] [PubMed] [Google Scholar]
  25. Vogelzang N. J. Continuous infusion chemotherapy: a critical review. J Clin Oncol. 1984 Nov;2(11):1289–1304. doi: 10.1200/JCO.1984.2.11.1289. [DOI] [PubMed] [Google Scholar]
  26. Weiden P. L., Einstein A. B., Rudolph R. H. Cisplatin bolus and 5-FU infusion chemotherapy for non-small cell lung cancer. Cancer Treat Rep. 1985 Nov;69(11):1253–1255. [PubMed] [Google Scholar]

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