Abstract
Recent publications support the use of preradiation chemotherapy in the treatment of selected primary brain tumors. In the pediatric population, this treatment strategy often delays radiotherapy and may improve the outcome in patients. This manuscript describes the use of a preradiation chemotherapy approach for adult patients with newly diagnosed glioblastoma multiforme. The main objective of this trial was to determine the feasibility of delivering up to 3 monthly cycles of a 72 h continuous simultaneous intravenous infusion of BCNU (40 mg/m2/day) and cisplatin (40 mg/m2/day). Patients were evaluated for tumor response or progression after each cycle. Following the completion of the chemotherapy treatments or evidence of tumor progression, patients underwent external beam radiotherapy. A dose of 45 Gy was delivered to the pretreatment tumor volume plus surrounding edema and a margin of 3.0 cm. An additional 14.4 Gy was delivered to the preoperative volume plus a 2 cm margin. Fifty patients were enrolled, 47 were eligible and analyzable. Overall, 79% of patients were able to complete at least 2 cycles of treatment, exceeding the predefined measure of feasibility. One patient achieved a complete response, 10 patients a partial response and 18 patients had stable disease at completion of the chemotherapy treatments. Twenty-four patients experienced grade 4 toxicity, mostly hematologic. All patients were able to undergo radiotherapy following chemotherapy. These results indicate that a preradiation strategy is feasible. Although responses to the chemotherapy were seen, a phase III trial is needed to determine whether this approach provides an advantage over standard treatment; such a phase III trial has been undertaken by ECOG.
Similar content being viewed by others
References
Walker MD, Green SB, Byar DP: Randomized comparisons of radiotherapy and nitrosoureas for the management of malignant glioma after surgery. N Engl J Med 303: 1323-1329, 1980
Walker MD, Alexander EJ, Hunt WE: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49: 333-343, 1978
Kristiansen K, Hagen S, Kollwvoid T: Combined modality therapy of operated astrocytomas Grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian glioblastoma study group. Cancer 47: 649-652, 1981
Halperin EC, Burger PC, Bullard DE: The fallacy of the localized supratentorial malignant glioma. Int J Radiat Oncol Biol Phys 15: 505-509, 1976
Salazar OM, Rubin P: The spread of glioblastoma as a determining factor in the radiation treated volume. Int J Radiat Oncol Biol Phys 1: 627-637, 1996
Burger PC, Heinz ER, Shibata T, Kleihues P: Topographic anatomy and CT correlations in the untreated glioblastoma multiforme. J Neurosurg 68: 698-704, 1988
Sheline GE: Radiotherapy for high-grade gliomas. Int J Radiat Oncol Biol Phys 18: 793-803, 1990
Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG: Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 16: 1405-1409, 1989
Marks JE: Ionizing radiation. In: Salcman M (ed) Neurobiology of Brain Tumors. Williams & Wilkins, Baltimore, 1991, pp 299-320
Fine HA, Dear KBG, Loeffler JS, Black PM, Canellos GP: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71: 2585-2597, 1993
Greenberg HS, Ensminger WD, Chandler WF: Intraarterial BCNU chemotherapy in the treatment of malignant gliomas of the central nervous system. J Neurosurg 61: 423-429, 1984
Duffner PK, Horowitz ME, Krishner JP et al: Post-operative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328: 1725-1731, 1993
Hanauske AR: New approaches to chemotherapy of brain tumors with or without radiation. Crit Rev Neurosurg 3: 45-49, 1993
Grossman SA, Wharam M, Sheidler V, Kleinberg L, Zeltzman M, Yue N et al: Phase II study of continuous infusion carmustine and cisplatin followed by cranial irradiation in adults with newly diagnosed high-grade astrocytoma. J Clin Oncol 15: 2596-2603, 1997
Gilbert MR, Lunsford LD, Kondziolka D: A phase II study of continuous infusion chemotherapy, external beam radiotherapy and local boost radiotherapy for malignant gliomas. (Abstract) Proc Amer Soc Clin Oncol 12: 176, 1993
Mehta CR, Patel NR: A network algorithm for the exact treatment of Fisher's exact test in rxc contingency tables. J Amer Stat Assoc 78: 427-434, 1983
Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Amer Stat Assoc 53: 457-481, 1958
Cox DR, Snell EJ: Analysis of Binary Data. 2nd edn., Chapman and Hall, London, 1970, pp 66-68
Cox DR: Regression models and life tables (with discussion). JR Stat Soc B (Methodol) 34: 187-220, 1972
Mantel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemoth Rep 50: 163-170, 1966
Shapiro WR, Green SB, Burger PC, Mahaley Jr MS, Selker RG, VanGilder JC et al: Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg 71: 1-9, 1989
Rutten EHJM: Radiation injury to the brain. In: Karim ABMF, Laws ERJ (eds) Glioma. Springer-Verlag, Heidelberg, 1991, pp 171-178
Volk PE, Dillon WP: Radiation injury of the brain. Amer J Neurol Radiol 12: 45-62, 1991
Poisson M, Pouillart P, Bataini JP, Mashaly R, Pertuisset BF, Metzger J: Malignant gliomas treated after surgery by combination chemotherapy and delayed irradiation. Acta Neurochir 51: 15, 1979
Grossman SA, Sheidler V, Weissman D, Ahn H, Gilbert MR: Continuous infusion therapy for primary brain tumors: A new approach with a high response rate. (Abstract) Proc Amer Soc Clin Oncol 6: 72, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gilbert, M., O'Neill, A., Grossman, S. et al. A Phase II Study of Preradiation Chemotherapy Followed by External Beam Radiotherapy for the Treatment of Patients with Newly Diagnosed Glioblastoma Multiforme: An Eastern Cooperative Oncology Group Study (E2393). J Neurooncol 47, 145–152 (2000). https://doi.org/10.1023/A:1006402123397
Issue Date:
DOI: https://doi.org/10.1023/A:1006402123397