Abstract
No standard of care for patients with recurrent glioblastoma has been defined since temozolomide has become the treatment of choice for patients with newly diagnosed glioblastoma. This has renewed interest in the use of nitrosourea-based regimens for patients with progressive or recurrent disease. The most commonly used regimens are carmustine (BCNU) monotherapy or lomustine (CCNU) combined with procarbazine and vincristine (PCV). Here we report our institutional experience with nimustine (ACNU) alone (n = 14) or in combination with other agents (n = 18) in 32 patients with glioblastoma treated previously with temozolomide. There were no complete and two partial responses. The progression-free survival (PFS) rate at 6 months was 20% and the survival rate at 12 months 26%. Grade III or IV hematological toxicity was observed in 50% of all patients and led to interruption of treatment in 13% of patients. Non-hematological toxicity was moderate to severe and led to interruption of treatment in 9% of patients. Thus, in this cohort of patients pretreated with temozolomide, ACNU failed to induce a substantial stabilization of disease in recurrent glioblastoma, but caused a notable hematotoxicity. This study does not commend ACNU as a therapy of first choice for patients with recurrent glioblastomas pretreated with temozolomide.
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References
Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330
Glioma Meta-analysis Trialist (GMT) Group (2002) Chemotherapy for high-grade glioma. Cochrane Database Syst Rev (Online):CD003913
Medical Research Council Brain Tumor Working Party (2001) Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol 19:509–518
Weller M, Muller B, Koch R et al (2003) Neuro-oncology working group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma. J Clin Oncol 21:3276–3284. doi:10.1200/JCO.2003.03.509
Kato H, Fujimura M, Kumabe T et al (2004) PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma. J Clin Neurosci 11:37–41. doi:10.1016/j.jocn.2002.09.001
Tanaka M, Shibui S, Nomura K et al (2001) Radiotherapy combined with nimustine hydrochloride and etoposide for malignant gliomas: results of a pilot study. Jpn J Clin Oncol 31:246–250. doi:10.1093/jjco/hye059
Wolff JE, Berrak S, Koontz Webb SE et al (2008) Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients. J Neurooncol 88:57–63. doi:10.1007/s11060-008-9533-5
Brandes AA, Tosoni A, Amista P et al (2004) How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology 63:1281–1284
Brandes AA, Turazzi S, Basso U et al (2002) A multidrug combination designed for reversing resistance to BCNU in glioblastoma multiforme. Neurology 58:1759–1764
Kappelle AC, Postma TJ, Taphoorn MJ et al (2001) PCV chemotherapy for recurrent glioblastoma multiforme. Neurology 56:118–120
Schmidt F, Fischer J, Herrlinger U et al (2006) PCV chemotherapy for recurrent glioblastoma. Neurology 66:587–589. doi:10.1212/01.wnl.0000197792.73656.c2
Macdonald DR, Cascino TL, Schold SC Jr et al (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280
Carson KA, Grossman SA, Fisher JD et al (2007) Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS consortium phase I and II clinical trials. J Clin Oncol 25:2601–2606. doi:10.1200/JCO.2006.08.1661
Wong ET, Hess KR, Gleason MJ et al (1999) Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572–2578
Lamborn KR, Yung WK, Chang SM et al (2008) Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. Neuro oncol 10:162–170. doi:10.1215/15228517-2007-062
Yung WK, Albright RE, Olson J et al (2000) A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer 83:588–593. doi:10.1054/bjoc.2000.1316
Wick A, Felsberg J, Steinbach JP et al (2007) Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma. J Clin Oncol 25:3357–3361. doi:10.1200/JCO.2007.10.7722
Vredenburgh JJ, Desjardins A, Herndon JEII et al (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729. doi:10.1200/JCO.2007.12.2440
Vredenburgh JJ, Desjardins A, Herndon JEII et al (2007) Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 13:1253–1259. doi:10.1158/1078-0432.CCR-06-2309
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Happold, C., Roth, P., Wick, W. et al. ACNU-based chemotherapy for recurrent glioma in the temozolomide era. J Neurooncol 92, 45–48 (2009). https://doi.org/10.1007/s11060-008-9728-9
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DOI: https://doi.org/10.1007/s11060-008-9728-9