RNOP-09: pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study.
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.


CONCLUSIONS
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.
Beier
Christoph P
CP
Department of Neurology, University of Regensburg, Universitätsstrasse 84, 93053 Regensburg, Germany. christoph.beier@gmx.de
Schmid
Christina
C
Gorlia
Thierry
T
Kleinletzenberger
Christine
C
Beier
Dagmar
D
Grauer
Oliver
O
Steinbrecher
Andreas
A
Hirschmann
Birgit
B
Brawanski
Alexander
A
Dietmaier
Christopher
C
Jauch-Worley
Tanja
T
Kölbl
Oliver
O
Pietsch
Torsten
T
Proescholdt
Martin
M
Rümmele
Petra
P
Muigg
Armin
A
Stockhammer
Günther
G
Hegi
Monika
M
Bogdahn
Ulrich
U
Hau
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D000077204:Temozolomide; D055815:Young Adult
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D003606:Dacarbazine; D004317:Doxorubicin; D000077204:Temozolomide