Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer

A randomized controlled trial for 7-year follow-up

Abstract

Background and aims

The efficacy of a biological response modifier polysaccharide K in adjuvant immunochemotherapy was evaluated in primary colon cancer patients with macroscopic Dukes' C after curative resection.

Patients and methods

Employing the minimization method using three factors (lymph node metastases, preoperative serum CEA level, and institution), 446 patients were allocated into groups P and C. Group P received immunochemotherapy, oral PSK (3 g per day) followed by oral 5-FU (200 mg/body per day), while group C received only intermittent chemotherapy, oral 5-FU (200 mg per day) followed by 4-week rest. Both groups received ten courses.

Results

Survival for cancer death was significantly higher in group P than in group C, but there was no difference in 7-year disease-free survival or overall survival had.

Conclusion

Repeated alternating administration with PSK followed by 5-FU can improve survival for cancer death.

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

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

References

  1. 1.

    Statistics and Information Department, Minister's Secretariat, Ministry of Health and Welfare (ed) (2000) Vital statistics of Japan 1998, vol 1. Foundation of Statistics of Public Welfare Association, Tokyo, Japan

  2. 2.

    Kobayashi H, Matsunaga K, Oguchi Y (1995) Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview. Cancer Epidemiol Biomarkers Prev 4:275–281

  3. 3.

    Ikuzawa M, Matsunaga K, Nishiyama S, Nakajima S, Kobayashi Y, Andoh T, Kobayashi A, Ohhara M, Ohmura Y, Wada T (1988) Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). Int J Immunopharmacol 10:415–423

  4. 4.

    Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 343:1122–1126

  5. 5.

    Yasutomi M (ed) (1997) Japanese classification of colorectal carcinoma, 6th edn. Japanese Society for Cancer of the Colon and Rectum. Kanehara, Tokyo

  6. 6.

    Nakazato H, Ito K, Takagi H, Saji S, Koike A, Baba S, Mai M, Ohashi Y, Sakamoto J (1999) A randomized clinical trial on adjuvant immunochemotherapy with protein bound polysaccharide K (PSK) after curative resection of colon cancer. Presented at Am Soc Clin Oncol Annual Meeting, Atlanta, 15–18 May

  7. 7.

    Shah A, MacDonald W, Goldie J, Gudauskas G, Brisebois B (1985) 5-FU Infusion in advanced colorectal cancer. A comparison of three dose schedules. Cancer Treat Rep 69:739–742

  8. 8.

    Koike A, Kojima T, Kanemitsu T, Kato K, Naruse T, Suzumura K, Matsumoto K, Yamamoto S (1990) Treatment of advanced colorectal and gastric carcinomas with a 48-hour infusion of 5-fluorouracil. J Cancer Res Clin Oncol [Suppl]116:660

  9. 9.

    Koike A, Matsumoto K, Suzumura K, Saegusa J, Inamura Y, Kojima T, Kato K, Kanemitsu T, Naruse T, Yamamoto S (1990) Efficacy of a 48-hour infusion of 5-fluorouracil in patients with Stage IV gastric cancer after palliative gastrectomy (in Japanese with English abstract). Jpn J Cancer Chemother 17:1309–1314

  10. 10.

    Moertel CG, O'Fallon JR, Go VLW, O'Connel MJ, Thynne GS (1986) The preoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of colorectal cancer. Cancer 58:603–610

  11. 11.

    Pocok SJ, Simon R (1975) Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 31:103–115

  12. 12.

    Freedman LS (1982) Tables of the number of patients required in clinical trials using the log-rank test. Stat Med 1:121–129

  13. 13.

    Takashima S, Kinami Y, Miyazaki I (1988) Clinical effect of postoperative adjuvant immunochemotherapy with FT-207 suppository and PSK for colo-rectal cancer patients (in Japanese with English abstract). Jpn J Cancer Chemother 15:2229–2236

  14. 14.

    Colorectal Cancer Chemotherapy Study Group of Japan (1995) Five-year result of a randomized controlled trial of adjuvant chemotherapy for curatively resected colorectal carcinoma. Jpn J Clin Oncol 25:91–103

  15. 15.

    Mitomi T, Tsuchiya S, Iijima N, Aso K, Suzuki K, Nishiyama K, Amano T, Takahashi T, Murayama N, Oka H (1992) Randomized, controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer. Dis Colon Rectum 35:123–130

  16. 16.

    Mitomi T, Tsuchiya S, Iijima N, Aso K, Nishiyama K, Amano T, Takahashi T, Oka H, Murayama N, Oya K, Noto T, Ogawa N (1993) Randomized controlled study on adjuvant immunochemotherapy with PSK in curatively resected colorectal cancer-5 years follow-up after surgery (a final report) (in Japanese with English abstract). J Jpn Soc Cancer Ther 28:71–83

  17. 17.

    Moertel CG, Fleming TR, McDonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA (1990) Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322:352–358

  18. 18.

    QUASAR Collaborative Group (2000) Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. Lancet 355:1588–1596

  19. 19.

    Currie GA, Bagshawe KD (1970) Active immunotherapy with corynebacterium parvum and chemotherapy in murine fibrosarcomas. BMJ 1:541–544

  20. 20.

    Kondo T, Sakamoto J, Ichihashi H, Kamei H (1981) Effect of alternating administration of PS-K and carbazilquinone in tumor-bearing mice. Gann 72:293–299

  21. 21.

    Kondo T, Ichihashi H, Nakazato H, Ogawa N (1989) Result of adjuvant immunochemotherapy on 8-year survival using Krestin and Futraful for gastric cancer patients who underwent radical gastrectomy—a randomized controlled trial by cooperative study group (in Japanese with English abstract). Biotherapy 3:655–664

  22. 22.

    Kondo T, Sakamoto J, Nakazato H (1991) Alternating immunochemotherapy of advanced gastric carcinoma: a randomized comparison of carbazilquinone and PSK to carbazilquinone in patients with curative gastric resection. Biotherapy 3:287–295

  23. 23.

    Nakazato H, Koike A, Saji S (1990) Evaluation of PSK for gastric cancer patients who underwent radical gastrectomy (in Japanese with English abstract). Biotherapy 4:884–891

  24. 24.

    Ogoshi K, Miyaji M, Nakamura K, Kondoh Y, Makuuchi H, Tajima T (1998) Immunotherapy and combined assay of serum levels of carcinoembryonic antigen and acute-phase reactants. Cancer Immunol Immunother 46:14–20

  25. 25.

    Kunieda K, Saji S, Tanemura H, Kato M, Sugiyama Y, Takao H, Umemoto T, Miya K, Azuma S, Furuta T (1992) Significance of preoperative serum IAP value for gastric cancer in terms of indication of postoperative BRM therapy (in Japanese with English abstract). J Jpn Soc Cancer Ther 27:1713–1721

  26. 26.

    Kidd PM (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 5:4–27

  27. 27.

    Kato M, Hirose K, Hakozaki M, Ohno M, Saito Y, Izutani R, Noguchi J, Hori Y, Okumoto S, Kuroda D (1995) Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide. Cancer Immunol Immunother 40:152–156

  28. 28.

    Noguchi K, Tanimura H, Yamaue H, Tsunoda T, Iwahashi M, Tani M, Mizobata S, Hotta T, Arii K, Tamai M (1995) Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro. Anticancer Res 15:255–258

  29. 29.

    Tsujitani S, Kakeji Y, Orita H, Watanabe A, Kohnoe S, Baba H, Anai H, Maehara Y, Sugimachi K (1992) Postoperative adjuvant immunochemotherapy and infiltration of dendritic cells for patients with advanced gastric cancer. Anticancer Res 12:645–648

  30. 30.

    Mizutani Y, Yoshida O (1991) Activation by the protein-bound polysaccharide PSK (Krestin) of cytotoxic lymphocytes that act on fresh autologous tumor cells and T24 human urinary bladder transitional carcinoma cell line in patients with urinary bladder cancer. J Urol 145:1082–1087

  31. 31.

    Kariya Y, Inoue N, Kihara T, Okamoto N, Sugie K, Mori T, Uchida A (1992) Activation of human natural killer cells by the protein-bound polysaccharide PSK independently of interferon and interleukin 2. Immunol Lett 31:241–246

Download references

Acknowledgements

We thank Ms. Atsuko Tanaka for the assistance in the preparation of the manuscript.

Author information

Correspondence to Katsuki Ito.

Additional information

The authors represent the Study Group of Immunochemotherapy with PSK for Colon Cancer

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ito, K., Nakazato, H., Koike, A. et al. Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. Int J Colorectal Dis 19, 157–164 (2004). https://doi.org/10.1007/s00384-003-0532-x

Download citation

Keywords

  • 5-Fluorouracil
  • Polysaccharide K
  • Colon cancer
  • Immunochemotherapy
  • Intermittent administration