Skip to main content
SpringerLink
Log in

Clinical trial of external beam-radiotherapy combined with daily administration of low-dose cisplatin for supratentorial glioblastoma multiforme – A pilot study

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

This trial tested the assumed efficacy and safety of externalbeam-radiotherapy combined with daily administration of low dose cisplatin(CDDP) (ERCLC therapy) for patients with glioblastoma multiforme (GBM).Thirty adult patients with supratentorial GBM received daily postoperativetreatment with low dose intravenous CDDP (4–6 mg/m2) administered30 minutes before external irradiation. In 10 patients, intraoperativeradiotherapy (IORT) following surgery was given prior to ERCLC therapy.Tumor response on MRI, interval to tumor progression, survival, andtoxicities were analyzed. None of the patients showed a tumor response toERCLC therapy. Overall, the median time to tumor progression was 6 monthswith a 1-year tumor progression-free rate of 26.7% and a 2-year rateof 0%. The median survival time was 15 months with a 1-year survivalrate of 69.9% and a 2-year rate of 31.5%. The survival rate ofpatients with IORT was better than that of those without IORT, however,there was no significant difference. Anorexia associated with nauseaoccurred in 70% and general fatigue in 10.0%. Leukopenia andthrombocytopenia occurred in 26.7% and 33.3%, respectively.However, none of the patients had to be withdrawn from therapy due to thesetoxicities. Other toxicities were not observed. This clinical study showedthat daily administration of low dose CDDP did not enhance tumor response toirradiation for GBM on MRI. Regarding toxicity, however, ERCLC therapy waswell tolerated. Although this trial did not provide sufficient data todetermine whether ERCLC therapy was effective for GBM due to the smallnumber of patients, additional clinical trials of this therapy may bewarranted because that the survival rate in this study was equal to thebetter results recently reported for newly diagnosed GBM.

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.

Institutional subscriptions

References

  1. Feun LG, Stewart DJ, Maor M, Leavens M, Savaraj N, Burgess MA, Yung WA, Benjamin RS: A pilot study of cisdiamminedichloroplatinum and radiation therapy in patients with high grade astrocytomas. J Neuro-Oncol 1: 109–113, 1983

    Google Scholar 

  2. Stewart DJ, O'Bryan RM, Al-Sarraf M, Costanzi JJ, Oishi N: Phase II study of cisplatin in recurrent astrocytomas in adults. A Southwest Oncology Group Study. J Neuro-Oncol 1: 145–147, 1983

    Google Scholar 

  3. Spence AM, Berger MS, Livingston RB, Ali-Osman F, Griffin B: Phase II evaluation of high-dose intra-venous cisplatin for treatment of adult malignant gliomas recurrent after chloroethyl-nitrosourea failure. J Neuro-Oncol 12: 187–191, 1992

    Google Scholar 

  4. Mortimer JE, Crowley J, Eyre H, Weiden P, Eltringham J, Stuckey WJ: Phase II randomized study comparing sequential and combined intraarterial cisplatin and radiation therapy in primary brain tumors. A Southwest Oncology Group Study. Cancer 69: 1220–1223, 1992

    Google Scholar 

  5. Hiesiger EM, Green SB, Shapiro WR, Burger PC, Selker RG, Mahaley MS Jr, Robertson JT, Hochberg FH, Young RF: Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A. J Neuro-Oncol 25: 143–154, 1995

    Google Scholar 

  6. Kiu M, Chang C, Cheng W, Lin T, Wong C, Tang SG, Leung W, Chen L, Ho Y, Ng K, Chen J, Yang T, Lai G: Combination chemotherapy with carmustine and cisplatin before, during, and after radiotherapy for adult malignant gliomas. J Neuro-Oncol 25: 215–220, 1995

    Google Scholar 

  7. Douple EB, Richmond RC: Platinum complexes as radiosensitizers of hypoxic mammalian cells. Br J Cancer 37: 98–102, 1978

    Google Scholar 

  8. Chibber R, Stratford IJ, O'Neill P, Sheldon PW, Ahmed, Lee B: The interaction between radiation and complexes of cis-Pt (II) and Ph (II): studies at the molecular and cellular level. Int J Radiat Biol 48: 513–524, 1985

    Google Scholar 

  9. Begg AC, Van der Kolf PJ, Dewit L, Bartelink H: Radiosensitization by cisplatin of RIF 1tumor cells in vitro. Int J Radiat Biol 50: 871–884, 1986

    Google Scholar 

  10. Keizer HJ, Karim ABMF, Njo KH, Tierie AH, Snow GB, Vermorken JB, Pinedo HM: Feasibility study on daily administration of cis-diamminedichloroplatinum (II) in combination with radiotherapy. Radiother Oncol 1: 227–234, 1984

    Google Scholar 

  11. Fujita M, Masaki N, Murayama S, Matayoshi Y, Ikeda H, Shimizutani K, Inoue T, Kozuka T: Radiotherapy combined with daily administration of low dose cisplatin for head and neck cancer. Study on serum concentrations of cisplatin and acute complications. J Jpn Soc Ther Radiol Oncol 2: 255–262, 1990

    Google Scholar 

  12. Schaake-Koning C, Van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, Renaud A, Rodrigus P, Schuster-Uitterhoeve L, Sculier J, van Zandwijk N, Bartelink H: Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N Engl J Med 326: 524–530, 1992

    Google Scholar 

  13. Milano G, Troger V, Courdi A, Fantana X, Chauvel P, Lagrange JL: Pharmacokinetics of cisplatin given at a daily low dose as a radiosensitizer. Cancer Chemother Pharmacol 27: 55–59, 1990

    Google Scholar 

  14. Yamada S, Takai Y, Nemoto K, Ogawa Y, Hoshi A, Mitsui H, Sakamoto K: Radiotherapy combined with daily low-dose cisplatin for esophageal carcinoma. A pilot study. Jpn J Cancer Chemother 21: 1689–1691, 1994

    Google Scholar 

  15. Begg AC, Behlken S, Bartelink H: The effect of cisplatin on the repair of radiation damage in RIF 1 mouse tumours in vitro. Radiother Oncol 15: 79–91, 1989

    Google Scholar 

  16. Trovo MG, Minatel E, Franchin G, Boccieri MG, Nascimben O, Bolzicco G, Pizzi G, Torretta A, Veronesi A, Gobitti C, Zanelli DJ, Monfardini S: Radiotherapy versus radiotherapy enhanced by cisplatin in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys 24: 11–15, 1992

    Google Scholar 

  17. Bader JL, Glatstein E: Extent beam radiation therapy of gliomas. In: Kornblith PL, Walker MD (eds) Advances in Neuro-Oncology. Futura Publishing Company, Inc., Mount Kisco, New York 347–386, 1988

    Google Scholar 

  18. Barker FB II, Prados MD, Chang SM, Gutin PH, Lamborn KR, Larson DA, Malec MK, McDermott MW, Sneed PK, Wara WM, Wilson CB: Radiation response and survival time in patients with glioblastoma multiforme. J Neurosurg 84: 442–448, 1996

    Google Scholar 

  19. Levin VA, Wara WM, Davis RL, Silver P, Pesser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB: NCOG protocol 6GL91: Response to treatment with radiation therapy and seven-drug chemotherapy in patients with glioblastoma multiforme. Cancer Treat Rep 70: 739–743, 1986

    Google Scholar 

  20. Bashir R, Hochberg FH, Linggood RM, Hottleman K: Preirradiation internal carotid artery BCNU in treatment of glioblastoma multiforme. J Neurosurg 68: 917–919, 1988

    Google Scholar 

  21. Mbidde EK, Selby PJ, Perren TJ, Dearnalaey DP, Whitton A, Ashley S, Workman P, Bloom HJG, McElwain TJ: High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiatherapy for grade IV astrocytoma. Br J Cancer 58: 779–782, 1988

    Google Scholar 

  22. Kinsella TJ, Collins J, Rowland J, Klecker R, Wright D, Katz D, Steinberg SM: Pharmacology and Phase I/II study of continuous intravenous infusion of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme. J Clin Oncol 6: 871–879, 1988

    Google Scholar 

  23. Roosen N, Kiwit JCS, Lins E, Schirmer M, Bock WJ: Adjuvant intraarterial chemotherapy with nimustine in the management of World Health Organization grade IV gliomas of the brain. Cancer 64: 1984–1994, 1989

    Google Scholar 

  24. Marcial-Vega VA, Wharam MD, Leibel S, Clark A, Zweig R, Order SE: Treatment of supratentorial high grade gliomas with split course high fractional dose postoperative radiotherapy. Int J Radiat Oncol Biol Phys 16: 1419–1424, 1989

    Google Scholar 

  25. Greiner R, Blattmann H, Thum P, Bosiger P, Coray A, Kann R, Lahtinen T, Reinhardt H, von Essen CF, Zimmerman A: Anaplastic astrocytoma and glioblastoma: Pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN). Radiother Oncol 17: 37–46, 1990

    Google Scholar 

  26. Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 Final report. Int J Radiat Oncol Biol Phys 18: 321–324, 1990

    Google Scholar 

  27. Sakai N, Yamada H, Andoh T, Hirata T, Nishimura Y, Miwa Y, Shimuzu K, Yanagawa S: Intraoperative radiation therapy for malignant glioma. Neurol Med Chir (Tokyo) 31: 702–707, 1991

    Google Scholar 

  28. Tobias JS, Smith BJ, Blackman G, Finn G: Concurrent daily cisplatin and radiotherapy in locally advanced squamous carcinoma of the head-and-neck and bronchus. Radiother Oncol 9: 263–268, 1987

    Google Scholar 

  29. van Harskamp G, Boven E, Vermorken JB, van Deutekom H, Stam J, Njo KH, Karim AB, Tierie AH, Golding RP, Pinedo HM: Phase II trial of combined radiotherapy and daily low-dose cisplatin for inoperable, locally advanced non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 13: 1735–1738, 1987

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Gifu University School of Medicine, Gifu, Japan

    Jun Shinoda, Noboru Sakai, Akira Hara, Tatsuya Ueda, Hideki Sakai & Kei Nakatani

Authors
  1. Jun Shinoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Noboru Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akira Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatsuya Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hideki Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kei Nakatani
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shinoda, J., Sakai, N., Hara, A. et al. Clinical trial of external beam-radiotherapy combined with daily administration of low-dose cisplatin for supratentorial glioblastoma multiforme – A pilot study. J Neurooncol 35, 73–80 (1997). https://doi.org/10.1023/A:1005816320920

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005816320920

Search

Navigation