An Outline of RAFP Therapy


The principles of surgical therapy for primary malignant brain tumors, especially malignant gliomas, were established by Cushing in the 1930s, but today more than half a century later, the survival rate following surgery in such cases has been extended by no more than a few months. The treatment of malignant gliomas thus remains one of the most difficult, unsolved problems in neurosurgery today.


Brain Tumor Malignant Glioma Malignant Brain Tumor Multicellular Spheroid Primary Malignant Brain Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aoki Y (1981) Radiotherapy combined with Tegafur (FT-207) for brain tumors. Jpn J Cancer Chemother 8: 624–632 (in Japanese)Google Scholar
  2. 2.
    Arakawa M, Shimizu F, Okada N (1974) Effect of 1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride on leukemia L-1210. Jpn J Cancer Res 65: 191Google Scholar
  3. 3.
    Asamura M, Saito T (1977) Cell synchronization and chemotherapy of cancer. Jpn J Cancer Chemother 5: 737–746 (in Japanese)Google Scholar
  4. 4.
    Bhuyan BK, Scheidt LG, Fraser TJ (1972) Cell-cycle phase specificity of antitumor agent. Cancer Res 32: 398–407PubMedGoogle Scholar
  5. 5.
    Blokhina NG, Vozny EK, Garin AM, (1972) Results of treatment of malignant tumors with Futrafur. Cancer 30: 390–392PubMedCrossRefGoogle Scholar
  6. 6.
    Fujita H, Ogawa K, Sawabe T, Kimura M (1972) Metabolism of N1-(2′-tetrahydrofuryl)-5-fluorouracil (FT-207). Jpn J Cancer Clin 18: 917–922 (in Japanese)Google Scholar
  7. 7.
    Fujita H, Ogawa K, Akimoto H, Tahira K, Fukunaga I, Takakura K, Kohono T, Kimura M (1976) Distribution of FT-207 and its active substance into the brain and cerebrospinal fluid. Jpn J Cancer Chemother 3: 551–555 (in Japanese)Google Scholar
  8. 8.
    Fujiwara K, Taomoto K, Tamaki N, Matsumoto S, Chihara T (1973) Uptake of FT-207 by the brain tumor and its clinical trials. Jpn J Cancer Chemother 5: 361–368 (in Japanese)Google Scholar
  9. 9.
    Hiller SA, Zhuk RA, Lidak MY (1967) Analogous of pyrimidine nucleosides 1. N-(α-furanydyl)-derivatives of natural pyrimidine bases and their antimetabolite. Dokl Akad Nauk (USSR) 176: 332–335Google Scholar
  10. 10.
    Hori M, Nakagawa H, Hasegawa H, Hayakawa T, Mogami H, Nakata Y (1978) Chemotherapy of brain tumor combined with radiotherapy. Neurol Med Chir (Tokyo) 18: 649–654 (in Japanese)CrossRefGoogle Scholar
  11. 11.
    Hoshino T, Barker M, Wilson CB, Boldrey EB, Fewer D (1972) Cell kinetics of human gliomas. J Neurosurg 37: 15–26PubMedCrossRefGoogle Scholar
  12. 12.
    Hoshino T (1973) Cell kinetics of brain tumor. Neurol Surg 1: 453–459 (in Japanese)Google Scholar
  13. 13.
    Hoshino T (1980) Chemotherapy of malignant brain tumors: Biology and pharmacokinetics. Neurol Surg 8: 1007–1016 (in Japanese)Google Scholar
  14. 14.
    Imagawa K, Tochio H, Toda M, Hayashi S, Asai A, Nomura R (1972) Clinical studies on PSK combined therapy with surgery and adjuvant chemotherapy for brain tumor. Shinyaku Rinsho 26: 2109–2113 (in Japanese)Google Scholar
  15. 15.
    Kanamaru R, Asamura M, Sato H, Saito S, Wakui A, Saito T (1980) Studies on mechanism of action of ACNU, l-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride: Effects on cultured Hela S3 cells. Tohoku J Exp Med 132: 431–441PubMedCrossRefGoogle Scholar
  16. 16.
    Kaneko S, Abe H, Aida T, Tsuru M, Kodama T, Kobayashi H (1980) Fundamental study of immunochemotherapy of brain tumors—Experimental brain tumor model and immunochemotherapy by a combination of PSK and ACNU. Neurol Med Chir (Tokyo) 20: 997–1005 (in Japanese)CrossRefGoogle Scholar
  17. 17.
    Kaneko S, Allen NJ, Clendenon NR, Kartha M (1983) Treatment schedule for combined therapy using radiation and ACNU in experimental brain tumors. Neurol Med Chir (Tokyo) 23: 849–855 (in Japanese)CrossRefGoogle Scholar
  18. 18.
    Kida Y, Shibuya N, Okada C, Umenura A, Kobayashi T, Kageyama N, Kamei H (1977) Immunological therapy for brain tumors by protein polysaccharide (PSK). Jpn J Cancer Chemother 4: 863–867 (in Japanese)Google Scholar
  19. 19.
    Kitahara M, Katakura R, Mori T, Suzuki J, Sasaki T (1984) Combined effect of ACNU and 5-fluorouracil on spheroids of rat glioma cells. Neurol Med Chir (Tokyo) 24: 747–757 (in Japanese)CrossRefGoogle Scholar
  20. 20.
    Kitahara M, Katakura R, Mori T, Suzuki J, Sasaki T (1986) Combined effect of ACNU and 5-Fu on rat glioma cells in spheroids and monolayer cultures. Int J Cancer 38: 215–222PubMedCrossRefGoogle Scholar
  21. 21.
    Kitahara M, Katakura R, Suzuki J, Sasaki T (1987) Experimental combination chemotherapy of ACNU and 5-Fu against cultured glioma model (spheroid) and subcutaneous rat glioma. Int J Cancer 40: 557–563PubMedCrossRefGoogle Scholar
  22. 22.
    Kitahara M, Katakura R, Mashiyama S, Niizuma H, Yoshimoto T, Suzuki J, Mori T, Wada T (1987) Results of oligodendroglioma combined with radiochemotherapy. Neurol Surg 15: 397–403 (in Japanese)Google Scholar
  23. 23.
    Kitahara M, Katakura R, Shingai J, Niizuma H, Yashimoto T, Suzuki J, Mori T, Wada T (1987) Clinical results of supratentorial low-grade astrocytoma combined with radio-chemotherapy. Neurol Surg 15: 597–604 (in Japanese)Google Scholar
  24. 24.
    Kohno T, Shitara N, Takakura K, Fujita H (1976) Role of FT-207 in the treatment of metastatic brain tumors. Jpn J Cancer Chemother 3: 729–734 (in Japanese)Google Scholar
  25. 25.
    Kohno T, Matsutani M, Hoshino T, Takakura K (1985) Effects of anticancer drugs on multicellular spheroids of 9L rat brain tumor. Brain and Nerve 37: 991–997 (in Japanese)PubMedGoogle Scholar
  26. 26.
    Kuwahara K, Katakura R, Sasaki T, Suzuki J (1987) Effect of combined treatment of X-rays and 5-Fu on rat glioma cells in multicellular spheroids. Neurol Med Chir (Tokyo) 27: (in press) (in Japanese)Google Scholar
  27. 27.
    Leenhouts HP, Chadwick KH (1980) An analysis of the interaction between two nitrosourea compounds and X-irradiation in rat brain tumor cells. Int J Radiat Biol 37: 169–181CrossRefGoogle Scholar
  28. 28.
    Matsumoto K, Tabuchi K, Furuta T (1983) Combination chemotherapy of brain tumors with ACNU and 5-Fu. Neurol Med Chir (Tokyo) 23: 625–632 (in Japanese)CrossRefGoogle Scholar
  29. 29.
    Matsuura H, Nakazawa S (1983) FT-207 and 5-Fu concentration in brain tumor tissues, plasma and CSF after administration of FT-207 suppository. Jpn J Cancer Chemother 11: 912–916 (in Japanese)Google Scholar
  30. 30.
    Mineura K, Mori T, Katakura R, Suzuki J (1979) Follow-up study of glioblastoma—A review of 179 cases. Neurol Med Chir (Tokyo) 19: 229–237 (in Japanese)CrossRefGoogle Scholar
  31. 31.
    Mineura K, Mori T, Katakura R, Sasaki T (1981) Therapeutic effects of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and radiation on the rat glioma. Neurol Surg 9: 257–265 (in Japanese)Google Scholar
  32. 32.
    Mitomi T, Ogoshi K(1987) PSK and clinical application. The Saishin-Igaku 42: 314–318 (in Japanese)Google Scholar
  33. 33.
    Miyaji C, Ogawa Y, Imajo Y, Kimura S (1982) Combination therapy of radiation and immunomodulators in the treatment of MM46 tumor transplanted C3H/He mice. J Jpn Soc Cancer Ther 17: 1035–1042 (in Japanese)Google Scholar
  34. 34.
    Muraoka K (1983) ACNU delivery to malignant brain tumor tissue and serum—route of administration and effect of phenobarbital. Brain and Nerve 35: 1199–1206 (in Japanese)PubMedGoogle Scholar
  35. 35.
    Mori T, Fukawa O, Sato T, Hori S, Wada T (1977) Regression of recurrent malignant glioma by combined chemoradiotherapy utilizing Carboquone, FT-207 and Telecobalt— Report of a case. Neurol Surg 5: 865–869 (in Japanese)Google Scholar
  36. 36.
    Mori T, Mineura K, Katakura R (1979) Chemotherapy of malignant brain tumor by a water-soluble anti-tumor nitrosourea, ACNU. Neurol Med Chir (Tokyo) 19: 1157–1171 (in Japanese)CrossRefGoogle Scholar
  37. 37.
    Mori T, Mineura K, Katakura R (1979) A consideration on pharmacokinetics of a new water-soluble anti-tumor nitrosourea, ACNU, in patients with malignant brain tumor. Brain and Nerve 31: 601–606 (in Japanese)PubMedGoogle Scholar
  38. 38.
    Nakagawa H, Hori M, Hasegawa H, Mogami H, Hayakawa T, Nakata Y (1979) The anti-tumor effet of ACNU and X-irradiation on mouse glioma. Brain and Nerve 31: 927–936 (in Japanese)PubMedGoogle Scholar
  39. 39.
    Nakao H, Fukushima M, Shimizu F (1974) Antileukemic agents: III. Synthesis and antitumor activity of N-(2-chloroethyl)-N-nitrosourea derivatives. Yakugaku Zasshi 94: 1032–1037 (in Japanese)Google Scholar
  40. 40.
    Nogaki H, Taomoto K, Tamaki N, Matsumoto S (1983) 5-FU concentration in brain tumors after co-administration of FT and uracil. Jpn J Cancer Chemother 10: 1007–1012 (in Japanese)Google Scholar
  41. 41.
    Phillips TL (1979) Current status, opportunities and problems in clinical combined chemoradiotherapy. Radiat Res, Proc of IVth international congress of radiation research, Tokyo, pp 822–829Google Scholar
  42. 42.
    Saito Y, Takami M, Muraoka K, Hokama Y (1981) Postoperative immuno-chemo-therapy of brain tumors which ACNU and PSK. Jpn J Cancer Chemother 8: 1066–1075 (in Japanese)Google Scholar
  43. 43.
    Saito Y, Hori T, Takami M, Muraoka K, Hokama Y, Numata H (1984) Long-term survival of brain tumor patients treated postoperatively with ACNU and PSK, and immunological follow-up. Jpn J Cancer Chemother 11: 2185–2192 (in Japanese)Google Scholar
  44. 44.
    Saito T, Yokoyama M, Himori T, Ujiie S, Sugawara N, Sugiyama Z, Kitada K (1977) Phase I and preliminary phase II study of l-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) administered by intermittent dose schedule. Jpn J Cancer Chemother 5: 991–1004 (in Japanese)Google Scholar
  45. 45.
    Sano K (1976) Chemotherapy on brain tumors. Neurol Med Chir (Tokyo) 16: 379–386 (in Japanese)Google Scholar
  46. 46.
    Shitara N (1978) Experimental and clinical study of cellular synchronization-radiation therapy for malignant brain tumors. Adv Neurol Sci 22: 119–131 (in Japanese)Google Scholar
  47. 47.
    Skipper HE, Schabel EM Jr, Mellet LB, Montgomery JA, Wekoff LJ, Lloid HH, Brockman RW (1970) Implications of biochemical cytokinetic pharmacologic and toxicologic relationships in the design of optimal therapeutic schedules. Cancer Chemother Rep 54: 431–450PubMedGoogle Scholar
  48. 48.
    Sueyoshi K, Uozumi A, Majima H (1979) Clinical experience with nitrosourea and FT-207. Suppository combination therapy against glioma. Jpn J Cancer Chemother 6: 1083–1088 (in Japanese)Google Scholar
  49. 49.
    Sueyoshi K, Majima H (1983) Cerebrospinal fluid distribution of systemically administered fluorinated pyrimidines. Jpn J Cancer Chemother 10: 818–823 (in Japanese)Google Scholar
  50. 50.
    Sugiyama S, Mori T, Suzuki J, Sasaki T (1984) Lethal effect of X-ray and ACNU on cultured rat glioma cells in multicellular spheroids. Neurol Med Chir (Tokyo) 24: 758 – 766 (in Japanese)Google Scholar
  51. 51.
    Sugiyama S, Mori T, Suzuki J, Sasaki T (1985) Effect of combined treatment, X-rays and ACNU on rat glioma cells in monolayer and multicellular spheroids. Neurol Med Chir (Tokyo) 25: 707–714 (in Japanese)Google Scholar
  52. 52.
    Suzuki M, Mori T, Watanabe T, Katakura R, Suzuki J, Wada T (1983) Combined radio-chemo-immunotherapy (RAFP therapy) for medulloblastoma. Surg Neurol 11: 1271–1276 (in Japanese)Google Scholar
  53. 53.
    Suzuki Y, Tanaka R (1980) Anti-tumor effect of ACNU on experimental mouse brain tumors. Neurol Med Chir (Tokyo) 20: 405–413 (in Japanese)Google Scholar
  54. 54.
    Takakura K (1979) Chemotherapy on brain tumors. Neurol Med Chir (Tokyo) 19: 933–940CrossRefGoogle Scholar
  55. 55.
    Takakura K, Sano K, Hojo S, Hirano A (1982) Metastatic tumors of the central nervous system. Igaku-Shoin, TokyoGoogle Scholar
  56. 56.
    Tanaka R, Murakami N, Suzuki Y, Takeda N, Arai H, Konno K, Tanimura K (1984) Radiotherapy using bleomycin, ACNU and vincristine for malignant brain tumors. Neurol Med Chir (Tokyo) 24: 557–563 (in Japanese)Google Scholar
  57. 57.
    Tsukagoshi S, Hashimoto Y, Fujii G, (1984) Krestin (PSK). Cancer Treatment Reviews 11:131–155PubMedCrossRefGoogle Scholar
  58. 58.
    Tsuchida T, Watanabe E, Nakayama H, Sasaki R, Nakamura M, Sasaki M, Fujiwara T, Nemoto S, Fujiwara K, Yagihashi M, Hayakawa I, Nomura K (1980) FAR therapy in brain tumors—FT-207—vitamin A—radiation therapy, Neurol Med Chir (Tokyo) 20: 453–461 (in Japanese)Google Scholar
  59. 59.
    Ushio Y, Abe H, Suzuki J, Tanaka R, Kitamura K, Miwa T, Matsutani M, Takeuchi K, Takakura K, Nomura K, Yamamoto S, Kageyama N, Handa H, Mogami H, Matsumoto S, Nishimoto A, Uozumi T, Hori T, Mori T, Mori K, Matsukado Y (1985) Evaluation of ACNU alone and combined with Tegafur as addition to radiotherapy for the treatment of malignant gliomas—A cooperative clinical trial. Brain and Nerve 37: 999–1006 (in Japanese)Google Scholar
  60. 60.
    Wakui A (1982) Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas. Jpn J Cancer Chemother 9: 1327–1338 (in Japanese)Google Scholar
  61. 61.
    Yamada Y, Kitazato K, Unemi N (1979) Combination treatment with Futraful and Krestin. Jpn J Cancer Chemother 6: 127–131 (in Japanese)Google Scholar
  62. 62.
    Yamamoto H, Nakamura O, Kohno T, Shitara N, Takakura K, Sano K, Maehara T, Akanuma A, Sato F (1984) Synchronization chemotherapy for malignant gliomas. Neurol Surg 12: 795–805 (in Japanese)Google Scholar
  63. 63.
    Yamamoto H, Matsutani M (1981) Cell kinetic studies on synchronized glioma cells in vitro with special reference to the mode of action of chemotherapeutic agents. Brain and Nerve 33: 781–793 (in Japanese)Google Scholar

Copyright information

© Springer-Verlag Tokyo 1988

Authors and Affiliations

  • T. Mori

There are no affiliations available

Personalised recommendations