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Treatment of recurrent malignant glioma with BCNU-fluosol and oxygen inhalation. A phase I-II study

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Abstract

Objectives: To evaluate the toxicity and response rate following BCNU with oxygen inhalation and escalatingdosages of fluosol administered to patients with radiographic progression of malignant glioma after definitivesurgery and radiotherapy. Method: This single arm, phase I-II multicenter trial, enrolled 99 patients withmalignant gliomas recurrent after definitive surgery and radiotherapy. All patients received a fixed dose(200 mg/m2) of BCNU along with 100% oxygen and fluosol, a perfluorochemical. Fluosol doses were escalat-edbetween patients (150, 275, 400 and 600 ml/m2). Treatment was repeated every 6 weeks for a maximum of 6cycles. Patients were assessed for toxicity at the time of infusion and sequentially thereafter. Response wasevaluated clinically and radiologically at least every 6 weeks. Results: Treatment was well tolerated. Dosereductions were required at least once in 18 patients, treatment delays were necessary at least once in 33patients. Grade 3-4 leukopenia occurred in 6 patients (12 events), grade 3-4 thrombocytopenia in 10 patients(25 events) and grade 3-4 liver enzymes elevations in 18 patients (31 events). Higher fluosol dosages did notproduce increases in toxicity or responses. Response or stabilization was seen in 57% (38% were stabiliza-tions)of the patients who entered the trial with progressive disease. The median time to progression was 45weeks, and median survival was 66 weeks for patients who had response or stabilization. For patients withglioblastoma response/stabilization was seen in 45% with a mean duration of 24 weeks, for patients withanaplastic astrocytoma response/stabilization was seen in 68% with a mean duration of 50 weeks. Conclusion:This treatment regimen is well tolerated. Our results suggest fluosol may enhance the effectiveness of BCNUfor the treatment of recurrent malignant gliomas. Future studies will be performed using fluosol at the dose of400 ml/m2.

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References

  1. Mahaley M: Neuro-oncology index and review (adult primary brain tumors). Radiotherapy, chemotherapy, immunotherapy, photodynamic therapy. J Neuro-Oncol 11: 85–147, 1991

    Google Scholar 

  2. Levin V, Gutin P, Leibel S: Neoplasm of the central nervous system. In: De Vita V, Hellman S, Rosenberg S (eds) Cancer. Principles and Practice of Oncology. 4th edition. J.B. Lippincott Co., Philadelphia, Pennsylvania 1679–1737, 1993

    Google Scholar 

  3. Blasberg R, Groothuis D: Chemotherapy of brain tumors: physiological and pharmacokinetic considerations. Sem Oncol 13 (1): 70–82, 1986

    Google Scholar 

  4. Kennedy K, Teicher B, Rockwell S et al.: The hypoxic tumor cell: a target for selective cancer chemotherapy. Biochem Pharmacol 29: 1–8, 1980

    Google Scholar 

  5. Berger N: Alkylating agents. In: De Vita V, Hellman S, Rosenberg S (eds) Cancer. Principles and Practice of Oncology. 4th edition. J.B. Lippincott Co., Philadelphia, Pennsylvania 400–408, 1993

    Google Scholar 

  6. Teicher B, Holden S, Jacobs J: Approaches to defining the mechanism of enhancement by Fluosol-DA 20% with carbogen of melphalan antitumor activity. Cancer Res 47: 513–518, 1987

    Google Scholar 

  7. Fine H, Dear K, Loeffler J et al.: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71 (8): 2585–2597, 1993

    Google Scholar 

  8. Levin V: Clinical pharmacology of the nitrosoureas. In: Prestayko A, Baker L, Crooke S, Carter S, Schein P (eds) Nitrosoureas. Current Status and New Developments. Academic Press, New York 171–180, 1981

    Google Scholar 

  9. Geyer R: Oxygen transport in vivoby means of perfluorochemical preparations. N Engl J Med 307: 304–306, 1982

    Google Scholar 

  10. Kuwamura K, Kokunai T, Tamaki N et al.: Synergistic effect of perfluorochemicals on BCNU chemotherapy. J Neurosurg 57: 467–471, 1982

    Google Scholar 

  11. Burger P, Vogel F et al.: Glioblastoma multiforme and anaplastic astrocytoma: pathologic criteria and prognostic implications. Cancer 56: 1106–1111, 1985

    Google Scholar 

  12. Hishikawa-Itoh Y, Kato T, Niwa T et al.: Minimal effective dose of perfluorochemical emulsion as a radiosensitizer. Nippon Gan Chiryo Gakkai Shi 24: 1243–1248, 1989 (in Japanese)

    Google Scholar 

  13. 13. Macdonald D, Cascino T, Schold C et al.: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8: 1277–1280, 1990

    Google Scholar 

  14. Walker M, Alexander E, Hunt W et al.: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative trial. J Neurosurg 49: 333–343, 1978

    Google Scholar 

  15. Walker M, Green S, Byar D et al.: Randomized comparison of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303: 1323–1329, 1980

    Google Scholar 

  16. Green S, Byar D, Walker M et al.: Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep 67: 121–132, 1983

    Google Scholar 

  17. Shapiro W, Green S, Burger P et al.: Randomized trial of three chemotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg 71: 1–9, 1989

    Google Scholar 

  18. De Vita V, Carbone P, Owens A et al.: Clinical trials with 1,3-Bis-(2-chloroethyl)-1-nitrosourea, NSC-409962. Cancer Res 25: 1876–1881, 1965

    Google Scholar 

  19. Phillips G, Wolff S, Fay J: Intensive 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) monochemotherapy and autologous marrow transplantation for malignant glioma. J Clin Oncol 4: 639–645, 1986

    Google Scholar 

  20. Levin V, Phuphanich S, Liu H-C et al.: Phase II study of combined BCNU, 5-Fluorouracil, hydroxyurea, and 6-mercaptopurine (BFHM) for the treatment of malignant gliomas. Cancer Treat Rep 70: 1271–1274, 1986

    Google Scholar 

  21. Prados M, Rodriguez L, Chamberlain M et al.: Treatment of recurrent gliomas with 1,3-Bis(2-chloroethyl)-1-Nitrosourea and Difluoromethylornithine. Neurosurgery 24: 806–809, 1989

    Google Scholar 

  22. Levin V, Prados M, Davis R et al.: Treatment of recurrent gliomas with a polydrug protocol designed to combat nitrosourea resistance. J Clin Oncol 10: 766–771, 1992

    Google Scholar 

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Authors and Affiliations

  1. Massachusetts General Hospital, Boston, Massachusetts

    Fred Hochberg & Raul Valenzuela

  2. Brain Tumor Research Center, University of California, San Francisco, San Francisco, California

    Michael Prados

  3. Kenneth Norris Jr Cancer Hospital and LA County/USC Medical Center, Los Angeles, California

    Christy Russell

  4. Milwaukee County Medical Complex, Milwaukee, Wisconsin

    David Weissman

  5. University of Kansas Medical Center, Kansas City, Kansas

    Richard Evans

  6. Brooklyn Hospital and New York University Medical School, USA

    Perry Cook

  7. Louisiana State University Medical Center, Shreveport, Louisiana

    Gary Burton

  8. Marin Oncology Associates, Ross, California

    Peter D. Eisenberg

  9. Alpha Therapeutic Corporation, Los Angeles, California, USA

    Lev Verkh

Authors
  1. Fred Hochberg
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  2. Michael Prados
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  3. Christy Russell
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  4. David Weissman
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  5. Richard Evans
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  6. Perry Cook
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  7. Gary Burton
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  8. Peter D. Eisenberg
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  9. Raul Valenzuela
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  10. Lev Verkh
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Hochberg, F., Prados, M., Russell, C. et al. Treatment of recurrent malignant glioma with BCNU-fluosol and oxygen inhalation. A phase I-II study. J Neurooncol 32, 45–55 (1997). https://doi.org/10.1023/A:1005727204169

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  • DOI: https://doi.org/10.1023/A:1005727204169

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