Abstract
Temozolomide (TMZ) is the standard of care for patients with newly diagnosed glioblastoma (GBM) as well as those with recurrent anaplastic glioma (AG) and GBM. It has become common practice to re-expose patients to TMZ who had been previously treated with TMZ, or to switch patients to alternative dosing regimens of TMZ when there are signs of relapse or progress on standard TMZ therapeutic regimens. To date, however, there is a scarcity of data on the efficacy of this therapeutic strategy, currently referred to as TMZ rechallenge. We have conducted a retrospective review of patients with recurrent glioma rechallenged with TMZ. Patients experiencing progressive disease (PD) during TMZ therapy who were rechallenged with alternative TMZ regimens and patients rechallenged after stable disease in a TMZ-free interval were evaluated separately. A total of 90 rechallenges were identified in 80 patients. The progression-free survival at 6 months (PFS-6) was 48% in patients with AG (12/25) and 27.7% in those with GBM (14/47). The PFS-6 was 16.7% in AG and 26.3% in GBM for patients switched during TMZ and 57.9 and 28.6% in patients rechallenged after a TMZ-free interval of at least 8 weeks. Relevant hematological toxicity (NCI-CTC grade 3–5) was observed in 22 of 90 rechallenges, and relevant non-hematological in ten of 90 rechallenges. Temozolomide was well tolerated and generated promising PFS-6 in patients who had previously failed TMZ, regardless if they progressed during TMZ treatment, or if they were rechallenged after a TMZ-free interval. These results suggest that the TMZ rechallenge strategy warrants further investigation in a prospective randomized trial.
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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
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
Yung WK, Prados MD, Yaya-Tur R et al (1999) Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol 17:2762–2771
Hau P, Koch D, Hundsberger T et al (2007) Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma. Neurology 68:688–690
Tuettenberg J, Grobholz R, Korn T, Wenz F, Erber R, Vajkoczy P (2005) Continuous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. J Cancer Res Clin Oncol 131:31–40
Wick W, Steinbach JP, Kuker WM, Dichgans J, Bamberg M, Weller M (2004) One week on/one week off: a novel active regimen of temozolomide for recurrent glioblastoma. Neurology 62:2113–2115
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
Brandes AA, Tosoni A, Cavallo G et al (2006) Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO). Br J Cancer 95:1155–1160
Tosoni A, Cavallo G, Ermani M et al (2006) Is protracted low-dose temozolomide feasible in glioma patients? Neurology 66:427–429
Tolcher AW, Gerson SL, Denis L et al (2003) Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011
Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003
Franceschi E, Omuro AM, Lassman AB, Demopoulos A, Nolan C, Abrey LE (2005) Salvage temozolomide for prior temozolomide responders. Cancer 104:2473–2476
Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280
Hoffman WF, Levin VA, Wilson CB (1979) Evaluation of malignant glioma patients during post-irradiation period. J Neurosurg 50:624–628
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
Carson KA, Grossman SA, Fisher JD, Shaw EG (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
Perry JR, Mason WP, Belanger K et al (2008) The temozolomide RESCUE study: a phase II trial of continuous (28/28) dose-intense temozolomide (TMZ) after progression on conventional 5/28 day TMZ in patients with recurrent malignant glioma. J Clin Oncol 26:S15 abstract 2010
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We thank Schering-Plough International for proof-reading of the paper.
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Wick, A., Pascher, C., Wick, W. et al. Rechallenge with temozolomide in patients with recurrent gliomas. J Neurol 256, 734–741 (2009). https://doi.org/10.1007/s00415-009-5006-9
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DOI: https://doi.org/10.1007/s00415-009-5006-9