CLINICAL STUDY – PATIENT STUDY Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma Ufuk Abacioglu • Hale B. Caglar • Perran F. Yumuk • Zuleyha Akgun • Beste M. Atasoy • Meric Sengoz Received: 2 June 2010 / Accepted: 13 September 2010 / Published online: 29 September 2010 Ó Springer Science+Business Media, LLC. 2010 Abstract The current standard therapy for newly diag- nosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m 2 for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1–14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8–4.2) and the median OS was 7 months (95% CI 5.1–8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7–32.2) and the 1-year OS rate was 12% (95% CI -1–25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3–4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high- grade glioma previously treated with temozolomide. Keywords Protracted Á Temozolomide Á High-grade glioma Á Glioblastoma Introduction High-grade gliomas are the most frequent malignant brain tumors seen in adults and usually have a poor prognosis. For a long time, the mainstay treatment of these tumors has been radiotherapy (RT) followed by alkylating agents such as nitrosoureas, procarbazine, and, more recently, temozolomide. Temozolomide is an oral alkylating agent with 100% bioavailability [1]. It is well tolerated and has activity against high-grade gliomas. Temozolomide was first approved for the treatment of recurrent high-grade gliomas at a dose of 150–200 mg/m 2 for 5 consecutive days every 28-day cycle (standard 5-day regimen) [1–3]. This dosing schedule was based on schedule-dependent activity of the drug in preclinical and Phase I studies in the late 1980s and 1990s [1, 4, 5]. Currently, the standard treatment for newly diagnosed glioblastoma is multimodality therapy including maximal surgical resection and adjuvant RT concurrent with ClinicalTrials.gov Identifier: NCT00575887. U. Abacioglu (&) Á H. B. Caglar Á Z. Akgun Á B. M. Atasoy Radiation Oncology Department, Marmara University Hospital, Tophanelioglu Cad. 13/15 Altunizade, 34660 Istanbul, Turkey e-mail: ufuk@abacioglu.com P. F. Yumuk Medical Oncology Division, Marmara University Hospital, Istanbul, Turkey M. Sengoz Radiation Oncology Department, Acibadem Kozyatagi Hospital, Istanbul, Turkey 123 J Neurooncol (2011) 103:585–593 DOI 10.1007/s11060-010-0423-2