A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma

Purpose. - To evaluate the maximum tolerated dose of simultaneous integrated -boost intensity modulated radiotherapy (SIB-IMRT) associated with temozolomide in patients with glioblastoma. Patients and methods. - Between November 2009 and January 2012, nine patients with malignant glioma were enrolled in this phase I clinical trial. Radiotherapy was delivered using fractions of 2.5 Gy on the planning target volume b and of 1.9 Gy on the planning target volume a. Volumes were defined as follow: gross tumour volume b: tumour taking up contrast on T1 weighted MRI images; clinical target volume b: gross tumour volume b + 0.5 cm (adapted to the anatomical structures) and lastly planning target volume b: clinical target volume b + 0.5 cm; gross tumour volume a: tumour (gross tumour volume b)+ 2 cm and including oedema outlined on T2Flair MRI sequences; clinical target volume a gross tumour volume a + 0.5 cm (adapted to the anatomical structures); planning target volume a: clinical target volume a + 0.5 cm. Three patients were enrolled at each of the three levels of dose (70, 75 and 80 Gy prescribed on the planning target volume b and 56, 60 and 60.8 Gy on the planning target volume a). Radiotherapy was delivered with temozolomide according to the standard protocol. Dose-limiting toxicities were defined as any haematological toxicities at least grade 4 or as any radiotherapy-related non-haematological acute toxicities at least grade 3, according to the Common Terminology Criteria for Adverse Events, version 3.0. Results. - Until the last dose level of 80 Gy, no patient showed dose-limiting toxicity. Conclusions. - SIB-IMRT, at least until a dose of 80 Gy in 32 daily fractions, associated with temozolomide is feasible and well tolerated. (C) 2016 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.