1. RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study
- Author
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Dagmar Beier, Alexander Brawanski, Oliver Kölbl, Tanja Jauch-Worley, Torsten Pietsch, Armin Muigg, Birgit Hirschmann, G. Stockhammer, Christopher Dietmaier, Andreas Steinbrecher, Ulrich Bogdahn, Thierry Gorlia, Christina Schmid, Petra Rümmele, Christine Kleinletzenberger, Christoph P. Beier, Peter Hau, Martin Proescholdt, Monika E. Hegi, and Oliver Grauer
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_treatment ,Dacarbazine/analogs & derivatives ,610 Medizin ,Phases of clinical research ,Polyethylene Glycols/adverse effects ,Doxorubicin/analogs & derivatives ,Polyethylene Glycols ,Central Nervous System Neoplasms ,Surgical oncology ,ddc:610 ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Combined Modality Therapy ,Dacarbazine ,Drug Therapy, Combination ,Female ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,macromolecular substances ,lcsh:RC254-282 ,Drug Administration Schedule ,Central Nervous System Neoplasms/radiotherapy ,Young Adult ,Internal medicine ,Genetics ,medicine ,Temozolomide ,Humans ,Doxorubicin ,Progression-free survival ,Glioblastoma/radiotherapy ,Aged ,business.industry ,technology, industry, and agriculture ,Surgery ,Radiation therapy ,Regimen ,business ,Glioblastoma - Abstract
Background Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. Methods 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. Results 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. Conclusion 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 Trial registration clinicaltrials.gov NCT00944801.
- Published
- 2009