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Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer

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Abstract

Non-specific immunopotentiators, such as polysaccharide K (PSK), also known as OK-432, induce anti-tumor effects via immunological responses. The efficacy of combination immunochemotherapy using these immunopotentiators has been examined by multiple previous studies. The survival benefits of immunochemotherapy for patients with curative resections of gastric cancers are not widely accepted. To clarify this issue, we performed a meta-analysis to evaluate the effect of immunochemotherapy on survival in patients with curative resections of gastric cancer. For this study, we compared the results of chemotherapy and immunotherapy using the biological response modifier PSK as an immunopotentiator. The meta-analysis included 8,009 patients from eight randomized controlled trials after central randomization. The overall hazard ratio for eligible patients was 0.88 (95% confidence interval, 0.79–0.98; P = 0.018) with no significant heterogeneity [χ 2(8) for heterogeneity = 11.7; P = 0.16]. The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK improves the survival of patients after curative gastric cancer resection.

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References

  1. Ferlay J, Bray F, Pisani P et al (2004) GLOBOCAN 2002. Cancer incidence, mortality and prevalence worldwide. IARC CancerBase No. 5, version 2.0. IARC, Lyon

  2. Sastre J, García-Saenz JA, Díaz-Rubio E (2006) Chemotherapy for gastric cancer. World J Gastroenterol 12:204–213

    PubMed  CAS  Google Scholar 

  3. 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

    PubMed  CAS  Google Scholar 

  4. Ohno R, Yamada K, Masaoka T et al (1984) A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation. Cancer Immunol Immunother 18:149–154

    Article  PubMed  CAS  Google Scholar 

  5. Sakamoto J, Morita S, Oba K et al (2006) Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials. Cancer Immunol Immunother 55:404–411

    Article  PubMed  CAS  Google Scholar 

  6. Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet 343:1122–1126

    Article  PubMed  CAS  Google Scholar 

  7. Nakajima T, Inokuchi K, Hattori T et al (1989) Multi-institutional cooperative study of adjuvant immunochemotherapy in gastric cancer—five-year survival rate (in Japanese). Gan To Kagaku Ryoho 16:799–806

    PubMed  CAS  Google Scholar 

  8. Kim R, Yoshida K, Toge T (2002) Current status and future perspectives of post-operative adjuvant therapy for gastric carcinoma. Anticancer Res 22:283–289

    PubMed  CAS  Google Scholar 

  9. Ikuzawa M, Matsunaga K, Nishiyama S et al (1988) Fate and distribution of an antitumor protein-bound polysaccharide PSK (Krestin). Int J Immunopharmacol 10:415–423

    Article  PubMed  CAS  Google Scholar 

  10. Higgins JPT, Green S (eds) (2005) Assessment study quality. Cochrane handbook for systematic reviews of interventions 4.2.5 [updated May 2005]; Section 6. The Cochrane Library, Issue 3. Wiley, Chichester, UK

  11. Parmar MB, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834

    Article  PubMed  CAS  Google Scholar 

  12. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  13. Niimoto M, Hattori T, Tamada R, Sugimachi K, Inokuchi K, Ogawa N (1988) Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. Jpn J Surg 18:681–686

    CAS  Google Scholar 

  14. 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). Biotherapy 3:655–664

    Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. Ogawa M, Kako H, Kitano T et al (1994) Cooperative study of adjuvant immunochemotherapy using HUFU (Mifurol®) for gastric cancer patients who underwent curative resection (in Japanese). Rinsyo To Kenkyu 71:201–206

    Google Scholar 

  17. Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet 343:1122–1126

    Article  PubMed  CAS  Google Scholar 

  18. Ochiai T, Sato H, Sato H et al (1983) Randomly controlled study of chemotherapy versus chemoimmunotherapy in postoperative gastric cancer patients. Cancer Res 43:3001–3007

    PubMed  CAS  Google Scholar 

  19. Fujimoto S, Furue H, Kimura T et al (1984) Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer—a randomized controlled trial. Jpn J Surg 14:286–292

    Article  PubMed  CAS  Google Scholar 

  20. Kanabe S, Tamakuma S, Mimura K et al (1985) Comparison of immunochemotherapy and chemotherapy of stage IV gastric carcinoma (in Japanese). Gan No Rinsho 31:1805–1809

    PubMed  CAS  Google Scholar 

  21. Sato S (1989) Study of validation of post-operative adjuvant chemotherapy following curative resection of stage II, III gastric cancer (in Japanese). Tokyo Ika Daigaku Zasshi 47:297–308

    Google Scholar 

  22. Nio Y, Tobe T (1989) Immunity of gut-associated lymphoid tissue and the role of the oral immunotherapy in multi-disciplinary treatment of the digestive organ cancer (in Japanese). Nippon Geka Gakkai Zasshi 90:1436–1438

    PubMed  CAS  Google Scholar 

  23. Imaizumi M, Kondo T, Kamei H, Ichihashi H (1990) Cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer (II). Cooperative study group on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer supported by the Ministry of Health and Welfare (Kondo’s group) (in Japanese). Gan to Kagaku Ryoho 17:2397–2403

    PubMed  CAS  Google Scholar 

  24. Fujimoto S, Furue H, Kimura T et al (1991) Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: a randomised controlled study. Eur J Cancer 27:1114–1118

    Article  PubMed  CAS  Google Scholar 

  25. Maehara Y, Sugimachi K, Akagi M, Kakegawa T, Shimazu H, Tomita M (1992) Early postoperative chemotherapy following noncurative resection for patients with advanced gastric cancer. Br J Cancer 65:413–416

    PubMed  CAS  Google Scholar 

  26. Imaizumi M, Kondo T, Kamei H (1994) Cooperative study of postoperative long-term adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer (second trial) (in Japanese). Gan No Rinsho 40:1243–1250

    Google Scholar 

  27. Tanaka N, Aichi A, Nagata H et al (1995) Preoperative intra tumor biological response modifier injection therapy for patients with stomach neoplasm (in Japanese). Nihon Rinsho Meneki Gakkai Kaishi 18:626

    PubMed  CAS  Google Scholar 

  28. Osawa S, Shiroto H, Kondo Y, et al (1996) Randomized controlled study on adjuvant immunochemotherapy with carmofur (HCFU) for noncuratively resected and unresected gastric cancer (in Japanese). Gan To Kagaku Ryoho 23:327–331

    PubMed  CAS  Google Scholar 

  29. Imaizumi M, Kondo T, Kamei H, Ichihashi H (1984) Cooperative studies on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer (in Japanese). Gan to Kagaku Ryoho 11:60–68

    PubMed  CAS  Google Scholar 

  30. Nakajima T, Inokuchi K, Hattori T, et al (1985) A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (in Japanese). Gan To Kagaku Ryoho 12:1850–1863

    PubMed  CAS  Google Scholar 

  31. Tamada R, Inokuchi K, Hattori T et al (1987) A multi-institutional study on postoperative adjuvant immunochemotherapy of gastric cancer (II) (in Japanese). Gan to Kagaku Ryoho 14:716–722

    PubMed  CAS  Google Scholar 

  32. Niimoto M, Hattori T, Tamada R, Sugimachi K, Inokuchi K, Ogawa N (1987) Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for curatively resected cases of gastric cancer. In: Salmon SE (ed) Adjuvant therapy of cancer V. Grune & Stratton, Orlando, pp 515–524

  33. Ichihashi H, Kondo T, Nakazato H (1987) Clinical results of a randomized controlled trial on the effect of adjuvant immunochemotherapy using Esquinon and Krestin in patients with curatively resected gastric cancer—7-year survival—Cooperative Study Group for Cancer Immunochemotherapy, Tokai Gastrointestinal Oncology Group (in Japanese). Gan to Kagaku Ryoho 14:2758–2766

    PubMed  CAS  Google Scholar 

  34. Nakazato H, Koike A, Ichihashi H, Saji S, Danno M, Ogawa N (1989) An effect of adjuvant immunochemotherapy using krestin and 5-FU on gastric cancer patients with radical surgery (first report)—a randomized controlled trial by the cooperative study group. Study Group of Immuno-chemotherapy with PSK for Gastric Cancer (in Japanese). Gan to Kagaku Ryoho 16:2563–2576

    PubMed  CAS  Google Scholar 

  35. Nakazato H, Koike A, Ichihashi H (1989) Results of a randomized controlled trial using adjuvant immunochemotherapy in patients surgically treated for gastric cancer (in Japanese). Biotherapy 3:1356–1360

    Google Scholar 

  36. Sakaguchi Y, Moriguchi S, Maehara Y et al (1989) Effect of postoperative long-term cancer chemotherapy (PLCC) on 15 year survival rate of gastric cancer patients (in Japanese). Biotherapy 3:1353–1355

    Google Scholar 

  37. Hattori T, Nakajima T, Nakazato H et al (1990) Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy. Jpn J Surg 20:127–136

    Article  PubMed  CAS  Google Scholar 

  38. Kondo M (1994) Immunotherapy as adjuvant treatment after curative resection of gastric cancer [comment]. Lancet 344:274

    Article  PubMed  CAS  Google Scholar 

  39. Mitomi T, Ogoshi K (1986) Clinical study of PSK as an adjuvant immunochemotherapeutic agent against gastric cancer (in Japanese). Gan To Kagaku Ryoho 13:2532–2537

    PubMed  CAS  Google Scholar 

  40. Saji S, Takao H, Kida H et al (1987) Effects of postoperative adjuvant immunochemotherapy using PSK for patients of gastric cancer, and its preventive effects on the recurrence (in Japanese). Prog Med 7:1703–1709

    Google Scholar 

  41. Maehara Y, Moriguchi S, Sakaguchi Y et al (1990) Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection. J Surg Oncol 45:169–172

    Article  PubMed  CAS  Google Scholar 

  42. Maehara Y, Emi Y, Sakaguchi Y et al (1990) Postoperative long-term cancer chemotherapy (PLCC) is effective for patients with gastric cancer following curative resection (in Japanese). Nippon Geka Gakkai Zasshi 9:1368–1370

    Google Scholar 

  43. Maehara Y, Inutsuka S, Takeuchi H, Baba H, Kusumoto H, Sugimachi K (1993) Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer. Cancer Chemother Pharmacol 33:171–175

    Article  PubMed  CAS  Google Scholar 

  44. Nakao I, Yokoyama T, Urushizaki I et al (1985) Clinical outcome of PSK for advanced gastric cancer (in Japanese). Oncologia 14:163–169

    Google Scholar 

  45. Nakazato H, Ichihashi H, Kondo T (1986) Clinical results of a randomized controlled trial on the effect of adjuvant immunochemotherapy using Esquinon and Krestin in patients with curatively resected gastric cancer. Cooperative Study Group of Cancer Immunochemotherapy, Tokai Gastrointestinal Oncology Group (in Japanese). Gan To Kagaku Ryoho 13:308–318

    PubMed  CAS  Google Scholar 

  46. Nakajima T, Inokuchi K, Hattori T et al (1989) Multi-institutional cooperative study of adjuvant immunochemotherapy in gastric cancer—five-year survival rate (in Japanese). Gan to Kagaku Ryoho 16:799–806

    PubMed  CAS  Google Scholar 

  47. Nio Y, Tsubono M, Tseng CC et al (1992) Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer (in Japanese). Biotherapy 4:117–128

    Article  PubMed  CAS  Google Scholar 

  48. Takahashi Y, Mai M, Nakazato H (2005) Preoperative CEA and PPD values as prognostic factors for immunochemotherapy using PSK and 5-FU. Anticancer Res 25:1377–1384

    PubMed  Google Scholar 

  49. Saji S, Kida T, Kunieda K et al (1985) Five-year survival of gastric cancer patients treated with postoperative long term adjuvant immunochemotherapy. Prog Med 5:485–492

    Google Scholar 

  50. Akimoto M, Nishihira T, Kasai M (1986) Modulation of the anti-tumor effect of BRM under various nutritional or endocrine conditions (in Japanese). Gan to Kagaku Ryoho 13:1270–1276

    PubMed  CAS  Google Scholar 

  51. Sugimachi K, Maehara Y, Ogawa M, Kakegawa T, Tomita M (1997) Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer. Cancer Chemother Pharmacol 40:233–238

    Article  PubMed  CAS  Google Scholar 

  52. Hanazaki K, Sodeyama H, Yokoyama S et al (1998) Postoperative chemotherapy may improve prognosis in unresectable gastric cancer. J Clin Gastroenterol 26:269–273

    Article  PubMed  CAS  Google Scholar 

  53. Kuroda Y, Horikawa N, Tsuji M et al (1998) Usefulness of polysaccharide K (PSK) as postoperative adjuvant immunotherapy in patients with stage IV gastric cancer. Int J Clin Oncol 3:311–316

    Google Scholar 

  54. Ogoshi K, Miyaji M, Iwata K, Kondo Y, Tajima T, Mitomi T (1990) Effect of postoperative adjuvant immunochemotherapy on panperitonitis carcimatous stomach cancer (in Japanese). Biotherapy 4:676–679

    Google Scholar 

  55. Sakamoto J, Koike A, Saji S, Teramukai S, Ohashi Y, Nakazato H (1992) Preoperative serum immunosuppressive acidic protein (IAP) test for the prognosis of gastric cancer: a statistical study of the threshold level and evaluation of the effect of the biological response modifier PSK. Jpn J Surg 22:530–536

    Article  CAS  Google Scholar 

  56. Toge T, Yamaguchi Y (2000) Protein-bound polysaccharide increases survival in resected gastric cancer cases stratified with a preoperative granulocyte and lymphocyte count. Oncol Rep 7:1157–1161

    PubMed  CAS  Google Scholar 

  57. Sakamoto J, Teramukai S, Nakazato H et al (2002) Efficacy of adjuvant immunochemotherapy with OK-432 for patients with curatively resected gastric cancer: a meta-analysis of centrally randomized controlled clinical trials. J Immunother 25:405–412

    Article  PubMed  CAS  Google Scholar 

  58. Algarra I, Collado A, Garrido F (1999) Protein bound polysaccharide PSK abrogates more efficiently experimental metastases derived from H-2 negative than from H-2 positive fibrosarcoma tumor clones. J Exp Clin Cancer Res 16:373–380

    Google Scholar 

  59. Nio Y, Tsubono M, Tseng CC et al (1992) Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer. Biotherapy 4:117–128

    Article  PubMed  CAS  Google Scholar 

  60. Pedrinaci S, Algarra I, Garrido F (1999) Protein-bound polysaccharide (PSK) induces cytotoxic activity in the NKL human natural killer cell line. Int J Clin Lab Res 29:135–140

    Article  PubMed  CAS  Google Scholar 

  61. Shibata M, Nezu T, Fujisaki S, Andou K, Tomita R, Fukuzawa M (2002) Clinical potential of biological response modifiers combined with chemotherapy for gastric cancer. Dig Surg 19:255–260

    Article  PubMed  CAS  Google Scholar 

  62. Ueda Y, Fujimura T, Kinami S et al (2006) A randomized phase III trial of postoperative adjuvant therapy with S-1 alone versus S-1 plus PSK for stage II/IIIA gastric cancer: Hokuriku-Kinki Immunochemo-Therapy Study Group-Gastric Cancer (HKIT-GC). Jpn J Clin Oncol [Epub ahead of print]

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Acknowledgments

The sponsor of this study had no role in data collection, data analysis, data interpretation, or writing this report. There were no funding sources. The corresponding author had full access to all data in this report and assumes final responsibility for the decision to submit this publication.

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Authors and Affiliations

  1. Department of Epidemiological and Clinical Research Information Management, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan

    Koji Oba

  2. Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, Japan

    Satoshi Teramukai

  3. Department of Surgery, Kochi University, Kochi, Japan

    Michiya Kobayashi

  4. Department of Surgery, Aichi Prefectural Hospital, Okazaki, Japan

    Takanori Matsui

  5. Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yasuhiro Kodera

  6. Young Leaders Program, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Junichi Sakamoto

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  1. Koji Oba
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  2. Satoshi Teramukai
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  3. Michiya Kobayashi
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  4. Takanori Matsui
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  5. Yasuhiro Kodera
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  6. Junichi Sakamoto
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Correspondence to Koji Oba.

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Oba, K., Teramukai, S., Kobayashi, M. et al. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer. Cancer Immunol Immunother 56, 905–911 (2007). https://doi.org/10.1007/s00262-006-0248-1

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