RNOP-09

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

Christoph P Beier, Christina Schmid, Thierry Gorlia, Christine Kleinletzenberger, Dagmar Beier, Oliver Grauer, Andreas Steinbrecher, Birgit Hirschmann, Alexander Brawanski, Christopher Dietmaier, Tanja Jauch-Worley, Oliver Kölbl, Torsten Pietsch, Martin Proescholdt, Petra Rümmele, Armin Muigg, Günther Stockhammer, Monika Hegi, Ulrich Bogdahn, Peter Hau

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftBMC Cancer
Vol/bind9
Sider (fra-til)308
ISSN1471-2407
DOI
StatusUdgivet - 2. sep. 2009
Udgivet eksterntJa

Fingeraftryk

temozolomide
Glioblastoma
Disease-Free Survival

Citer dette

Beier, Christoph P ; Schmid, Christina ; Gorlia, Thierry ; Kleinletzenberger, Christine ; Beier, Dagmar ; Grauer, Oliver ; Steinbrecher, Andreas ; Hirschmann, Birgit ; Brawanski, Alexander ; Dietmaier, Christopher ; Jauch-Worley, Tanja ; Kölbl, Oliver ; Pietsch, Torsten ; Proescholdt, Martin ; Rümmele, Petra ; Muigg, Armin ; Stockhammer, Günther ; Hegi, Monika ; Bogdahn, Ulrich ; Hau, Peter. / RNOP-09 : pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study. I: BMC Cancer. 2009 ; Bind 9. s. 308.
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title = "RNOP-09: pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study",
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.",
keywords = "Adolescent, Adult, Aged, Central Nervous System Neoplasms/diagnosis, Combined Modality Therapy, Dacarbazine/administration & dosage, Doxorubicin/administration & dosage, Drug Administration Schedule, Drug Therapy, Combination, Drug-Related Side Effects and Adverse Reactions, Female, Glioblastoma/diagnosis, Humans, Male, Middle Aged, Polyethylene Glycols/administration & dosage, Young Adult",
author = "Beier, {Christoph P} and Christina Schmid and Thierry Gorlia and Christine Kleinletzenberger and Dagmar Beier and Oliver Grauer and Andreas Steinbrecher and Birgit Hirschmann and Alexander Brawanski and Christopher Dietmaier and Tanja Jauch-Worley and Oliver K{\"o}lbl and Torsten Pietsch and Martin Proescholdt and Petra R{\"u}mmele and Armin Muigg and G{\"u}nther Stockhammer and Monika Hegi and Ulrich Bogdahn and Peter Hau",
year = "2009",
month = "9",
day = "2",
doi = "10.1186/1471-2407-9-308",
language = "English",
volume = "9",
pages = "308",
journal = "B M C Cancer",
issn = "1471-2407",
publisher = "BioMed Central",

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Beier, CP, Schmid, C, Gorlia, T, Kleinletzenberger, C, Beier, D, Grauer, O, Steinbrecher, A, Hirschmann, B, Brawanski, A, Dietmaier, C, Jauch-Worley, T, Kölbl, O, Pietsch, T, Proescholdt, M, Rümmele, P, Muigg, A, Stockhammer, G, Hegi, M, Bogdahn, U & Hau, P 2009, 'RNOP-09: pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study', BMC Cancer, bind 9, s. 308. https://doi.org/10.1186/1471-2407-9-308

RNOP-09 : pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study. / Beier, Christoph P; Schmid, Christina; Gorlia, Thierry; Kleinletzenberger, Christine; Beier, Dagmar; Grauer, Oliver; Steinbrecher, Andreas; Hirschmann, Birgit; Brawanski, Alexander; Dietmaier, Christopher; Jauch-Worley, Tanja; Kölbl, Oliver; Pietsch, Torsten; Proescholdt, Martin; Rümmele, Petra; Muigg, Armin; Stockhammer, Günther; Hegi, Monika; Bogdahn, Ulrich; Hau, Peter.

I: BMC Cancer, Bind 9, 02.09.2009, s. 308.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - RNOP-09

T2 - pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma--a phase II study

AU - Beier, Christoph P

AU - Schmid, Christina

AU - Gorlia, Thierry

AU - Kleinletzenberger, Christine

AU - Beier, Dagmar

AU - Grauer, Oliver

AU - Steinbrecher, Andreas

AU - Hirschmann, Birgit

AU - Brawanski, Alexander

AU - Dietmaier, Christopher

AU - Jauch-Worley, Tanja

AU - Kölbl, Oliver

AU - Pietsch, Torsten

AU - Proescholdt, Martin

AU - Rümmele, Petra

AU - Muigg, Armin

AU - Stockhammer, Günther

AU - Hegi, Monika

AU - Bogdahn, Ulrich

AU - Hau, Peter

PY - 2009/9/2

Y1 - 2009/9/2

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Central Nervous System Neoplasms/diagnosis

KW - Combined Modality Therapy

KW - Dacarbazine/administration & dosage

KW - Doxorubicin/administration & dosage

KW - Drug Administration Schedule

KW - Drug Therapy, Combination

KW - Drug-Related Side Effects and Adverse Reactions

KW - Female

KW - Glioblastoma/diagnosis

KW - Humans

KW - Male

KW - Middle Aged

KW - Polyethylene Glycols/administration & dosage

KW - Young Adult

U2 - 10.1186/1471-2407-9-308

DO - 10.1186/1471-2407-9-308

M3 - Journal article

VL - 9

SP - 308

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

ER -