Abstract
Purpose We performed a new phase II trial enrolling patients with newly diagnosed high-grade glioma (HGG) to test the efficacy of a weekly alternating temozolomide (TMZ) schedule after surgery and concomitant chemoradiotherapy. Methods From January 2005 to January 2007, 34 patients (21 men, 13 women; age range 30–70, mean age 53) were enrolled. There were 32 glioblastoma multiforme and two anaplastic astrocytoma. Each patient after surgery received standard concurrent chemoradiotherapy. After a 4-week break, patients were then to receive 12 cycles of 1-week-on/1-week-off TMZ, with 75 mg/m2 for the first cycle, 100 mg/m2 for the second, 125 mg/m2 for the third, and 150 mg/m2 from the fourth to the 12th. Hematological toxicity was monitored every week during concomitant chemoradiotherapy and then every 4 weeks. Results After 12 months from the end of radiotherapy, the overall survival (OS) rate was 59% (20/38), distributed as follows: 60% (18/30) for recursive partitioning analysis (RPA) class 4 patients and 33% (1/3) for RPA class 6 patients; the only RPA class 1 patient was alive and disease free at the time of writing. Median OS was 13 months [95% confidence interval (CI) 11.02–14.98 months]. Hematological toxicity was seen in six patients (18%): grade 1 neutropenia in four, grade 2 thrombocytopenia in one, and grade 4 thrombocytopenia plus grade 1 neutropenia in one. There was one case of opportunistic infection (Pneumocystis carinii pneumonitis). Conclusion The toxicity of the TMZ dose-dense regimen was very low. Results seem to be encouraging for RPA lower classes (patients with good prognostic factors).
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References
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330
Wick A, Felsberg J, Steinbach JP, Herrlinger U, Platten M, Blaschke B 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
Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A et al (2003) Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 88:1004–1011. doi:10.1038/sj.bjc.6600827
Wick W, Weller M (2005) How lymphotoxic is dose-intensified temozolomide? The glioblastoma experience. J Clin Oncol 23:4235–4236
Scott CB, Scarantino C, Urtasun R, Movsas B, Jones CU, Simpson JR et al (1998) Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90–06. Int J Radiat Oncol Biol Phys 40:51–55. doi:10.1016/S0360-3016(97)00485-9
Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB et al (2007) Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment. Clin Cancer Res 13:2038–2045. doi:10.1158/1078-0432.CCR-06-2149
Neyns B, van Mierlo B, Menten J, Dhondt L, Joosens E, Vastesaeger N et al (2005) A phase II study of temozolomide administered 21 out of 28 days for the treatment of patients with recurrent anaplastic (oligo) astrocytoma: an interim analysis of toxicity. J Clin Oncol 23:1560 Meeting abstracts
Tosoni A, Franceschi E, Ermani M, Bertorelle R, Bonaldi L, Blatt V, Brandes AA (2008) Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas. J Neurooncol [Epub ahead of print]
Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD et al (1999) Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572–2578
Soffietti R, Rudà R (2008) Neuro-oncology: new insights and advances in treatment. Lancet Neurol 7:14–16. doi:10.1016/S1474-4422(07)70305-8
Baruchel S, Diezi M, Hargrave D, Stempak D, Gammon J, Moghrabi A et al (2006) Safety and pharmacokinetics of temozolomide using a dose-escalation, metronomic schedule in recurrent paediatric brain tumours. Eur J Cancer 42:2335–2342. doi:10.1016/j.ejca.2006.03.023
Brada M, Judson I, Beale P, Moore S, Reidenberg P, Statkevich P et al (1999) Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br J Cancer 81:1022–1030. doi:10.1038/sj.bjc.6690802
Chinot OL, Barrié M, Fuentes S, Eudes N, Lancelot S, Metellus P et al (2007) Correlation between O6-methylguanine-DNA methyltransferase and survival in inoperable newly diagnosed glioblastoma patients treated with neoadjuvant temozolomide. J Clin Oncol 25:1459–1460. doi:10.1200/JCO.2006.07.4807
Brandes AA, Tosoni A, Cavallo G, Bertorelle R, Gioia V, Franceschi E 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. doi:10.1038/sj.bjc.6603376
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We thank Prof. R. Soffietti, Division of Neuro-oncology, Department of Neuroscience, University and San Giovanni Battista Hospital, Torino, Italy, for revising the manuscript.
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Dall’Oglio, S., D’Amico, A., Pioli, F. et al. Dose-intensity temozolomide after concurrent chemoradiotherapy in operated high-grade gliomas. J Neurooncol 90, 315–319 (2008). https://doi.org/10.1007/s11060-008-9663-9
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DOI: https://doi.org/10.1007/s11060-008-9663-9