RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study
1 Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany
2 EORTC Data Center, Avenue Mounierlaan 83/11, 1200, Brussels, Belgium
3 Department of Neurosurgery, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany
4 University of Applied Sciences Amberg Weiden, Hetzenrichter Weg 15, 92224 Weiden, Germany
5 Department of Radiooncology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany
6 Department of Neuropathology, University of Bonn, Sigmund-Freud-Strasse 3, 53015 Bonn, Germany
7 Department of Pathology, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany
8 Department of Neurology, University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
9 Laboratory of Brain Tumor Biology and Genetics, Centre Universitaire Romands de Neurochirurgie and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland
BMC Cancer 2009, 9:308 doi:10.1186/1471-2407-9-308Published: 2 September 2009
Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for.
In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression.
The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison.
Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data