Abstract
A meta-analysis and several studies of patients with grade III and IV gliomas have indicated that the addition of nitrosurea based chemotherapy to surgery and radiation may improve survival. We performed a phase II study of pre-irradiative chemotherapy with BCNU, cisplatin and etoposide. This implies a short total treatment duration and a reliable response evaluation.
The treatment schedule was three cycles of BCNU 200 mg/m2 i.v. on day 1, cisplatin 20 mg/m2 i.v. on day 1–5 and etoposide (VP-16) 100 mg/m2 i.v. on day 1–5, given every five weeks and followed by localized radiation, 60 Gy in 30 fractions. Twenty-nine patients with newly diagnosed glioblastoma multiforme (GBM), mean age 50 (27–66) and performance status (PS) 0–2 were included.
Using the Macdonald criteria 33% had partial remission (PR), 41% stable disease (SD) and 26% progressive disease (PD) after chemotherapy. After additional radiation 44% had PR, 37% SD and 19% PD. Non-hematological toxicity and leukopenia was mild, but thrombocytopenia (TP) frequent. Grade III and IV TP occurred in 25% and 57% respectively, and grade III bleeding in 45%. No severe or fatal complications was seen. Median time to progression (TTP) was 7.6 months (6.0–9.1) and median survival was 11.4 months (10.1–12.7).
We conclude that this regimen is effective and feasible in patients with GBM. The short course pre-irradiatory chemotherapy may be less cumbersome than adjuvant chemotherapy and the regimen may be even more active in grade III gliomas.
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References
Vecht CJ, Avezaat CJJ, van Putten WLJ et al.: The influence of the extent of surgery on the neurologial function and survival in malignant glioma. A retrospective analysis in 243 patients. J Neur Neurosurg Neuropsych 53: 466–471, 1990
Medical Research Council Brain Tumour Working Group: Prognostic factors for high-grade malignant gliomas: Development of a prognostic index. J Neuro-Oncol 9: 47–55, 1990
Walker MD, Green SB, Byar DP et al.: Randomized comparison of radiotherapy and nitrosureas for the treatment of malignant glioma after surgery. N Engl J Med 303: 1323–1329, 1980
Fine HA, Dear KBG, Loeffler JS et al.: Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 7l: 2585–2597, 1992
Jeremic B, Grujicic D, Jevremovic S et al.: Carboplatin and etoposide chemotherapy regimen for recurrent malignant glioma: a phase II study. J Clin Oncol 10: 1074–1077, 1992
Kiu M, Chang C, Cheng W et al.: Combination chemotherapy with carmustine and cisplatin before, during, and after radiotherapy for adult malignant gliomas. J Neuro-Oncol 25: 215–220, 1995
Fulton D, Urtasun R, Forsyth P: Phase II study of prolonged oral therapy with etoposide (VPl6) for patients with recurrent malignant glioma. J Neuro-Oncol 27: 149–155, 1996
Sanson M, Ameri A, Monjour A et al.: Treatment of recurrent malignant supratentorial gliomas with ifosfamide, carboplatin and etoposide: a phase II study. Eur J Cancer 32a: 2229–2235, 1996
Grossman SA, Wharam M, Sheidler V et al.: Phase II study of continuous infusion carmustine and cisplatin followed by cranial irradiation in adults with newly diagnosed highgrade astrocytoma. J Clin Oncol 15: 2596–2603, 1997
Forsyth PAJ, Petrov E, Mahallati H et al.: Prospective study of postoperative magnetic resonance imaging in patients with malignant gliomas. J Clin Oncol 15: 2076–2082, 1997
Macdonald DR, Cascino TL, Schold SC et al.: Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8: 1277–1280, 1990
Lagrange JL, Bondiau PY, Tessier E et al.: 1Tumoral platinum concentrations in patients treated with low-dose cisplatin as a radiosensitizer. Int J Cancer 68: 452–456, 1996
Chisholm RA, Stenning S, Hawkins TD: The accuracy of volumetric measurement of high-grade gliomas. Clin Oncol 40: 17–21, 1989
Curran WJ, Scott CB, Horton J et al.: Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst 85: 704–710, 1993
Stea B, Kittelson J, Cassady JR, Hamilton A, Guttikelch N, Lulu B, Obbens F, Rossman K, Shapiro W, Shetter A et al.: Treatment of malignant gliomas with interstitial irradiation and hyperthermia. Int J Radiat Oncol Biol Phys 24: 657–667, 1992
Sneed PK, Stauffer PR, McDermott MW, Diederich CJ, Lamborn KR, Prados MD, Chang S, Weaver KA, Spry L, Malec MK, Lamb SA, Voss B, Davis RL, Wara WM, LarsonDA, Phillips TL, Gutin PH: Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/-hyperthermia for glioblastoma multiforme. Int J Radiat Oncol Biol Phys 40: 287–295, 1998
Kirby S, Macdonald DR, Fisher B et al.: Pre-radiation chemotherapy for malignant gliomas in adults. Can J Neurol Sci 23: 123–127, 1996
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Lassen, U., Kristjansen, P.E., Wagner, A. et al. Treatment of Newly Diagnosed Glioblastoma Multiforme with Carmustine, Cisplatin and Etoposide Followed by Radiotherapy. A Phase II Study. J Neurooncol 43, 161–166 (1999). https://doi.org/10.1023/A:1006254716877
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DOI: https://doi.org/10.1023/A:1006254716877