Skip to main content

Advertisement

SpringerLink
Log in

Phase II study of S-1 as first-line treatment for elderly patients over 75 years of age with advanced gastric cancer: the Tokyo Cooperative Oncology Group study

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.

Methods

Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25–60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.

Results

Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7–37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.

Conclusions

The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Inoue M, Tsugane S (2005) Epidemiology of gastric cancer in Japan. Postgrad Med J 81:419–424

    Article  CAS  PubMed  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  3. Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S (2003) Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21:54–59

    Article  CAS  PubMed  Google Scholar 

  4. Boku N, Yamamoto S, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Kimura A, Ohtsu A (2007) Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912). Proc Am Soc Clin Oncol 25: abstract LBA4513

  5. Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, Fukushima M (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

    Article  CAS  PubMed  Google Scholar 

  6. 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

    CAS  PubMed  Google Scholar 

  7. Shirasaka T, Shimamoto Y, Fukushima M (1993) Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats. Cancer Res 53:4004–4009

    CAS  PubMed  Google Scholar 

  8. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M (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

    Article  CAS  PubMed  Google Scholar 

  9. Imamura H, Iishi H, Tsuburaya A, Hatake K, Imamoto H, Esaki T, Kato M, Furukawa H, Hamada C, Sakata Y (2008) randomized phase III study of irinotecan plus S-1 (IRIS) versus S-1 alone as first-line treatment for advanced gastric cancer (GC0301/TOP-002). Gastrointestinal Cancers Symposium: abstract 5

  10. Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T (1998) Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 34:1715–1720

    Article  CAS  PubMed  Google Scholar 

  11. Koizumi W, Kurihara M, Nakano S, Hasegawa K (2000) Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology 58:191–197

    Article  CAS  PubMed  Google Scholar 

  12. Japanese Gastric Cancer Association (1999) Japanese Classification of Gastric Carcinoma (In Japanese), 13th edn. Kanehara, Tokyo

    Google Scholar 

  13. Japanese Gastric Cancer Association (2001) Japanese classification of gastric carcinoma—2nd English edition—response assessment of chemotherapy and radiotherapy for gastric carcinoma: clinical criteria. Gastric Cancer 4:1–8

    Article  Google Scholar 

  14. Kurihara M, Aiko T (2001) The new Japanese classification of gastric carcinoma: revised explanation of “response assessment of chemotherapy and radiotherapy for gastric carcinoma”. Gastric Cancer 4:9–13

    Article  CAS  PubMed  Google Scholar 

  15. Cockcroft D, Gault H (1976) Prediction of clearance from serum creatinine. Nephron 16:31–41

    Article  CAS  PubMed  Google Scholar 

  16. Matsushima E, Yoshida K, Kitamura R, Yoshida K (1997) Determination of S-1 (combined drug of tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate) and 5-fluorouracil in human plasma and urine using high-performance liquid chromatography and gas chromatography-negative ion chemical ionization mass spectrometry. J Chromatogr B Biomed Sci Appl 691:95–104

    Article  CAS  PubMed  Google Scholar 

  17. Ishido K, Koizumi W, Tanabe S, Higuchi K, Sasaki T, Katada C, Azuma M, Saigenji K, Futawatari N, Saegusa M (2008) A patient with stage IV type 4 advanced gastric cancer who had a complete pathological response to short-term treatment with S-1 alone. Anticancer Drugs 19:921–925

    Article  CAS  PubMed  Google Scholar 

  18. Ikeda M, Furukawa H, Imamura H, Shimizu J, Ishida H, Masutani S, Tatsuta M, Kawasaki T, Satomi T (2002) Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor agent in animal model and in patients with impaired renal function. Cancer Chemother Pharmacol 50:25–32

    Article  CAS  PubMed  Google Scholar 

  19. Hirata K, Horikoshi N, Aiba K, Okazaki M, Denno R, Sasaki K, Nakano Y, Ishizuka H, Yamada Y, Uno S, Taguchi T, Shirasaka T (1999) Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug. Clin Cancer Res 5:2000–2005

    CAS  PubMed  Google Scholar 

  20. Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L, Verweij J, Van Glabbeke M, vO AT, Christian M, Gwyther S (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  21. Ohtsu A, Boku N, Yoshida S, Miyata Y, Shirao K, Shimada Y, Kurihara M (1998) Response of the primary lesion in gastric cancer o chemotherapeutic trials. Int J Clin Oncol 3:3–6

    Article  Google Scholar 

  22. Koizumi W, Kurihara M, Tanabe S, Kondo I, Yamazaki I, Nonaka M, Shimamura Y, Saigenji K (1999) Advantages of Japanese response criteria for estimating the survival of patients with primary gastric cancer. Gastric Cancer 2:14–19

    Article  PubMed  Google Scholar 

  23. Lee JL, Kang YK, Kang HJ, Lee KH, Zang DY, Ryoo BY, Kim JG, Park SR, Kang WK, Shin DB, Ryu MH, Chang HM, Kim TW, Baek JH, Min YJ (2008) A randomised multicentre phase II trial of capecitabine vs S-1 as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer. Br J Cancer 99:584–590

    Article  CAS  PubMed  Google Scholar 

  24. Graziano F, Santini D, Testa E, Catalano V, Beretta GD, Mosconi S, Tonini G, Lai V, Labianca R, Cascinu S (2003) A phase II study of weekly cisplatin, 6S-stereoisomer leucovorin and fluorouracil as first-line chemotherapy for elderly patients with advanced gastric cancer. Br J Cancer 89:1428–1432

    Article  CAS  PubMed  Google Scholar 

  25. Santini D, Graziano F, Catalano V, Di Seri M, Testa E, Baldelli AM, Giordani P, La Cesa A, Spalletta B, Vincenzi B, Russo A, Caraglia M, Virzi V, Cascinu S, Tonini G (2006) Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial. BMC Cancer 6:125

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the following investigators for their participation in the study: J Tanaka, H Niitani, K Nagao and T Nakajima. Thanks are also due to R Nagashima and M Kobayashi (TCOG) for help in preparing the report.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Gastrointestinal Oncology, Kitasato University School of Medicine, Kitasato University East Hospital, 2-1-1 Asamizodai, Sagamihara, Kanagawa, 228-8520, Japan

    Wasaburo Koizumi

  2. Gunma Prefectural Cancer Center, Gunma, Japan

    Toshikazu Akiya

  3. Showa University School of Medicine, Tokyo, Japan

    Atsushi Sato

  4. The Jikei University School of Medicine, Tokyo, Japan

    Toshikazu Sakuyama

  5. Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Eisaku Sasaki & Tsuneo Sasaki

  6. Nagaoka Chuo General Hospital, Niigata, Japan

    Takashi Tomidokoro

  7. Tobu Chiiki Hospital, Tokyo, Japan

    Tsutomu Hamada

  8. Kimitsu Chuo Hospital, Chiba, Japan

    Mototsugu Fujimori

  9. Center for Clinical Training and Education, School of Medicine, Toho University, Tokyo, Japan

    Yoshinori Kikuchi

  10. Showa University Northern Yokohama Hospital, Kanagawa, Japan

    Ken Shimada

  11. University of Tokai School of Medicine, Kanagawa, Japan

    Tetsuya Mine

  12. Saitama Cancer Center, Saitama, Japan

    Kensei Yamaguchi

  13. The Tokyo Cooperative Oncology Group, Tokyo, Japan

    Minoru Kurihara

Authors
  1. Wasaburo Koizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshikazu Akiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atsushi Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshikazu Sakuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eisaku Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Tomidokoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tsutomu Hamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mototsugu Fujimori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshinori Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ken Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tetsuya Mine
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kensei Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tsuneo Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Minoru Kurihara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wasaburo Koizumi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koizumi, W., Akiya, T., Sato, A. et al. Phase II study of S-1 as first-line treatment for elderly patients over 75 years of age with advanced gastric cancer: the Tokyo Cooperative Oncology Group study. Cancer Chemother Pharmacol 65, 1093–1099 (2010). https://doi.org/10.1007/s00280-009-1114-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-009-1114-6

Keywords

Search

Navigation