Adjuvant Chemotherapy of Gastric Cancer: JCOG Experience

  • Masatsugu Kitamura
  • Toshifusa Nakajima
  • Keiichiro Ohta
  • Atsushi Nashimoto
  • Yoshitaka Yamamura
  • Hiroshi Furukawa
  • Mitsuru Sasako
  • Taira Kinoshita
  • Hisahiko Motohashi
  • Yasuo Kunii


Results of treatment for gastric cancer in Japan have much improved over the last 20 years. The main reasons could be early detection of cancer and improvement in extended lymph node dissection. Multimodal therapy, including adjuvant chemotherapy, may also contribute to the improvement in prognosis [1]. Since the late 1950s, adjuvant chemotherapies have been routinely incorporated into postoperative therapy for gastric cancer in preventing postoperative recurrences. A review of past trials in Japan and Western countries, however, reveals little evidence of a survival benefit of postoperative adjuvant chemotherapy, though some favorable results have been reported in limited subsets of patients in Japan [2, 3, 4]. On the other hand, two meta-analyses showed statistical significance in terms of life prolongation with postoperative adjuvant chemotherapy [5,6]. To clarify the efficacy of postoperative adjuvant chemotherapy for gastric cancer, the Gastric Cancer Surgical Study Group (GCSSG) in the Japan Clinical Oncology Group (JCOG) [7] has initiated a new trial on the clinical significance of adjuvant chemotherapy.


Gastric Cancer Adjuvant Chemotherapy Gastric Cancer Patient Cytosine Arabinoside Postoperative Adjuvant Chemotherapy 
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  1. 1.
    Nakajima T, Nishi M (1988) Adjuvant chemotherapy, immunochemotherapy, and neoadjuvant chemotherapy for gastric cancer in Japan. In: Douglass HO (ed) Gastric cancer: contemporary issues in clinical oncology, vol 8. Churchill Livingstone, New York, pp 125–143Google Scholar
  2. 2.
    Imanaga H, Nakazato H (1977) Results of surgery for gastric cancer and effect of adjuvant mitomycin C on cancer recurrence. World J Surg 1:213–221CrossRefGoogle Scholar
  3. 3.
    Nakajima T, Fukami A, Takagi K, Kajitani T (1980) Adjuvant chemotherapy with mitomycin C, and with a multidrug combination of mitomycin C, 5-fluorouracil and cytosine arabinoside after curative resection of gastric cancer. Jpn J Clin Oncol 10:187–194Google Scholar
  4. 4.
    Nakajima T, Takahashi T, Takagi K, Kuno K, Kajitani T (1984) Comparison of 5-fluorouracil with futrafur in adjuvant chemotherapy with combined inductive and maintenance therapy for gastric cancer. J Clin Oncol 2:1366–1371PubMedGoogle Scholar
  5. 5.
    Hermans T, BonenKamp H (1994) Meta-analysis of adjuvant chemotherapy in gastric cancer: in reply. J Clin Oncol 12:879–880Google Scholar
  6. 6.
    Nakajima T, Ota K, Ishihara S, et al (1994) Meta-analysis of 10 postoperative adjuvant chemotherapies for gastric cancer in CIH. Jpn J Cancer Chemother 21:1800–1805Google Scholar
  7. 7.
    Shimoyama M, Fukuda H, Saijyo N, Ohyama S, Nishi M, Hamajima M (1998) Japan Clinical Oncology Group. Jpn J Clin Oncol 28:158–162PubMedCrossRefGoogle Scholar
  8. 8.
    Hugier PF, Destroyes JP, Baschet C (1980) Gastric carcinoma treated by chemotherapy after resection: a controlled study. Am J Surg 139:197–199CrossRefGoogle Scholar
  9. 9.
    Gastrointestinal Tumor Study Group (1982) Controlled trial of adjuvant chemotherapy following curative resection for gastric cancer. Cancer 49:1116–1122CrossRefGoogle Scholar
  10. 10.
    Alcobendas F, Milla A, Estape J, Curto J, Pera C (1983) Mitomycin C as an adjuvant treatment to resected gastric cancer. Ann Surg 198:13–17PubMedCrossRefGoogle Scholar
  11. 11.
    Higgins GA, Amadeo JH, Smith DE, Humphrey EW, Keehn RJ (1983) Efficacy of prolong intermittent therapy with combined 5-FU and methyl-CCNU following resection for gastric carcinoma. Cancer 52:1105–1112PubMedCrossRefGoogle Scholar
  12. 12.
    Engstrom PF, Lavin PT, Douglass HO, Brunner KW (1985) Postoperative adjuvant 5-fluorouracil plus methyl-CCNU therapy for gastric cancer patients. Cancer 55:1868–1873PubMedCrossRefGoogle Scholar
  13. 13.
    Schein PS, Lavin RC, Chlvers C (1985) For the international adjuvant trial in gastric cancer a controlled trial of FAM chemotherapy as adjuvant treatment for resected gastric carcinoma: an interim report. Proc ASCO 5:79Google Scholar
  14. 14.
    Jakesz R, Dittrich C, Funovics J, Hofbauer F, Rainer H, Reiner G, Schemper M, Schiessel R, Starlinger M (1988) The effect of adjuvant chemotherapy in gastric carcinoma is dependent on tumor histology: 5-year results of a prospective trial. Recent Results Cancer Res 110:44–51PubMedCrossRefGoogle Scholar
  15. 15.
    Allum W, Hallissey MT, Ward LC, Hockey MS (1989) A controlled prospective randomized trial of adjuvant chemotherapy in resectable gastric cancer: interim reports. Br J Cancer 60:739–744PubMedCrossRefGoogle Scholar
  16. 16.
    Coombes RC, Schein PS, Chivers CED, Wils J, Beretta G, Bliss A, Rutten A, Amadori D, Cortes-Funes H, Villar-Grimalt A, McArdle C, Raushecker HF, Boven E, Vassilopoulos P, Welvaart K, Ferreira EP, Wiig J, Gisselbrecht C, Rougier P, Woods EMA (1990) A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. J Clin Oncol 8:1362–1369PubMedGoogle Scholar
  17. 17.
    Krook JE, O’Connel MJ, Wieand HS, Beart JRW, Leigh JE, Kugler JW, Foley J, Pfeifle DM, Twito DI (1991) A prospective randomized evaluation of intensive course 5-fluorouracil, doxorubicin, and mitomycin C with no treatment in operable gastric cancer. Cancer 67:2454–2458PubMedCrossRefGoogle Scholar
  18. 18.
    MacDonald IS, Fleming TR, Peterson RF, Berenberg JL, McCure S, Chapman RA, Eyre HJ, Solanki D, Cruz AB, Gagliano R, Estes NC, Tangen CM, Rivkin S (1995) Adjuvant chemotherapy with 5-FU, Adriamycin, and mitomycin (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma. Ann Surg Oncol 2:488–494PubMedCrossRefGoogle Scholar
  19. 19.
    Tsavaris N, Tentas K, Kosmidis P, Sakelaropoulos N, Kosmas Ch, Lisaios B, Soumilas A, Mandrekas D, Tsetis A, Klonaris Ch.l (1996) A randomized trial comparing adjuvant fluorouracil, epirubicin and mitomycin with no treatment in operable gastric cancer. Chemotherapy 42:220–226PubMedCrossRefGoogle Scholar
  20. 20.
    Neri B, Leonardis VD, Romano S, Andreoli F, Pernice LM, Bruno L, Borrelli D, Valeri A, Fabbroni S, Intini C, Cini G (1996) Adjuvant chemotherapy after gastric resection in node-positive cancer patients: a multicenter randomized study. Br J Cancer 73:549–552PubMedCrossRefGoogle Scholar
  21. 21.
    Grau JT, Estape J, Fuster X, Filella J, Visa J, Teres G, Soler S, Albiol S, GarciA-Valdecas JC, Grande L, Bombi J, Bordas J, Alcobendas F (1998) Randomized trial of adjuvant chemotherapy with mitomycin plus futraful versus mitomycin alone in resected locally advanced gastric cancer. J Clin Oncol 16:1036–1039PubMedGoogle Scholar
  22. 22.
    Nakajima T, Kajitani T, Fukami A, Ohashi I (1976) Adjuvant chemotherapy of high dose mitomycin C for curatively resected gastric cancer (in Japanese). Gann no Rinsho 22:21–27Google Scholar
  23. 23.
    Nakajima T, Kajitani T (1980) Adjuvant chemotherapy with inductive multi-drug combination and long-term oral maintenance therapies for gastric cancer (in Japanese). J Jpn Soc Cancer Ther 15:980–988Google Scholar
  24. 24.
    Yamamura Y, Nishimura M, Sakamoto J, Yasui K, Morimoto T, Katoh T, Yasue M, Kito T, Miyaishi S, Nakazato H (1986) A randomized controlled trial of surgical adjuvant therapy with mitomycin C, 5-fluorouracil and OK-432 for patients suffering from gastric cancer. Jpn J Cancer Chemother 13:2134–2140Google Scholar
  25. 25.
    Fujii M, Sakabe T, Wakabayashi K, Kochi M, Mochizuki F, Kasakura Y, Yamagata M, Noro M, Osawa T, Iwai S, Tanaka T (1994) The optimal period for orally administered fluoropyrimidines as an adjuvant chemotherapy for gastric cancer: a pilot study using 5-FU tablets compared with surgical operation alone. Jpn J Cancer Chemother 21:1199–1208Google Scholar
  26. 26.
    Kimura T, Koyama Y (1981) Three prospective controlled study. Part 2 (in Japanese). Clinical Surgery 36:185–195Google Scholar
  27. 27.
    Kondo T, Inokuchi K, Hattori T, Inoue K, Taguchi T, Akiyama H, Abe O, Ito I, Nakajima T, Muto T, Kikuchi K, Kasai Y, Sugie S, Hayasaka A (1982) Multihospital randomized study on the adjuvant chemotherapy with mitomycin C and futraful for gastric cancer: estimation of five year survival rate. Jpn J Cancer Chemother 9:2025–2030Google Scholar
  28. 28.
    Taguchi T, Usugane M, Inokuchi K (1985) Randomized study on long-term adjuvant chemotherapy with futraful and mitomycin C for gastric cancer: a second study (fourth report) (in Japanese). Jpn J Cancer Chemother 12:1833–1839Google Scholar
  29. 29.
    Nakazato H, Koike A, Ichihashi H (1986) Postoperative adjuvant chemotherapy with carmofur for curatively resected gastric cancer. Gann no Rinsho 32:159–164Google Scholar
  30. 30.
    Arima S, Ohsato K, Hisatsugu T, Shimura H (1994) Multicenter randomized study of adjuvant chemotherapy with mitomycin C and tegafur or tegafur-uracil in gastric cancer. Eur J Surg 160:227–232PubMedGoogle Scholar
  31. 31.
    Maehara Y, Watanabe A, Kakeji Y, Baba H, Kohnoe S, Sugimachi K (1990) Postgastrectomy prescription of mitomycin C and UFT for patients with stage IV gastric cancer. Am J Surg 160:242–244PubMedCrossRefGoogle Scholar
  32. 32.
    Kubota T, Kumai K, Kitajima M, Fujisaki M, Yamada Y, Ushijima Y, Ishibiki K, Abe O (1994) Dose intensity of mitomycin C in adjuvant cancer chemotherapy for patients with gastric cancer. J Surg Oncol 57:40–45PubMedCrossRefGoogle Scholar
  33. 33.
    Nakazato H, Koike K, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 343:1122–1226PubMedCrossRefGoogle Scholar
  34. 34.
    Hagiwara A, Takahashi T, Kojima O (1992) Prophylaxis with carbon-absorbed mitomycin C against peritoneal recurrence of gastric cancer. Lancet 339:629–631PubMedCrossRefGoogle Scholar
  35. 35.
    Nakajima T, Okabayashi K, Nakazato H, Iwanaga T, Ota K, Kinoshita T, Kito T, Yamamura Y, Furukawa Y, Hiratsuka M (1994) Therapeutic effect of adjuvant chemotherapy consisted of MFC for curatively resected gastric cancer, a multicenter randomized controlled trial (in Japanese). J Jpn Soc Cancer Ther 29:654–662Google Scholar
  36. 36.
    Nakajima T, Nashimoto A, Kitamura M, Kito T, Iwanaga T Okabayashi M, Sasaki M, Ohta K, Sasaki J, Arai K, Yamamura Y, Furukawa H, Hiratsuka M, Sasako M, Sano T Kinoshita T, Goto Ml (submitted) Randomized trial of adjuvant chemotherapy with intravenous mitomycin C and 5-fluorouracil followed by oral UFT after curative surgery in serosa-intact gastric cancerGoogle Scholar
  37. 37.
    Metzger R, Leichman CG, Donenberg KD, Danenberg V, Lenz HJ, Hayashi K, Groshen S, Salonga D, Cohen H, Laren L, Peter Crookes, Silberman H, Baranda J, Konda B, Leichman L (1998) ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 16:309–316PubMedGoogle Scholar
  38. 38.
    Yonemura Y, Sowa T, Kinoshita K (1993) Neoadjuvant chemotherapy for high grade advanced gastric cancer. World J Surg 17:256–262PubMedCrossRefGoogle Scholar
  39. 39.
    Nakajima T, Ota K, Ishihara S (1997) Combined intensive chemotherapy and radical surgery for incurable gastric cancer. Ann Surg Oncol 4:203–208PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 1999

Authors and Affiliations

  • Masatsugu Kitamura
    • 1
  • Toshifusa Nakajima
    • 2
  • Keiichiro Ohta
    • 2
  • Atsushi Nashimoto
    • 3
  • Yoshitaka Yamamura
    • 4
  • Hiroshi Furukawa
    • 5
  • Mitsuru Sasako
    • 6
  • Taira Kinoshita
    • 7
  • Hisahiko Motohashi
    • 8
  • Yasuo Kunii
    • 9
  1. 1.Tokyo Metropolitan Bokuto HospitalTokyoJapan
  2. 2.Cancer Institute HospitalJapan
  3. 3.Niigata Cancer CenterJapan
  4. 4.Aichi Cancer CenterJapan
  5. 5.Center for Osaka Adult DiseaseJapan
  6. 6.National Cancer CenterJapan
  7. 7.National Cancer Center Higashi HospitalJapan
  8. 8.Kanagawa Cancer CenterJapan
  9. 9.National Sendai HospitalJapan

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