Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study

Kenneth F Hofland, Steinbjørn Hansen, Morten Sorensen, Silke Engelholm, Henrik P Schultz, Aida Muhic, Kirsten Grunnet, Anders Ask, Junia C Costa, Charlotte Kristiansen, Carsten Thomsen, Hans Skovgaard Poulsen, Ulrik Lassen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM.

MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity.

RESULTS: The response rate was 32% (95% CI 17-51%) for Bev-Tem (n = 32) and 23% (95% CI 9-44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable.

CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

OriginalsprogEngelsk
TidsskriftActa Oncologica
Vol/bind53
Udgave nummer7
Sider (fra-til)939-44
ISSN0284-186X
DOI
StatusUdgivet - jul. 2014

Fingeraftryk

irinotecan
temozolomide
Glioblastoma
Disease-Free Survival
Febrile Neutropenia
Adjuvant Radiotherapy
Bevacizumab

Citer dette

Hofland, Kenneth F ; Hansen, Steinbjørn ; Sorensen, Morten ; Engelholm, Silke ; Schultz, Henrik P ; Muhic, Aida ; Grunnet, Kirsten ; Ask, Anders ; Costa, Junia C ; Kristiansen, Charlotte ; Thomsen, Carsten ; Poulsen, Hans Skovgaard ; Lassen, Ulrik. / Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study. I: Acta Oncologica. 2014 ; Bind 53, Nr. 7. s. 939-44.
@article{ef339ffdcd054750ab03546e26d77846,
title = "Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study",
abstract = "BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM.MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30{\%} or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity.RESULTS: The response rate was 32{\%} (95{\%} CI 17-51{\%}) for Bev-Tem (n = 32) and 23{\%} (95{\%} CI 9-44{\%}) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable.CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.",
author = "Hofland, {Kenneth F} and Steinbj{\o}rn Hansen and Morten Sorensen and Silke Engelholm and Schultz, {Henrik P} and Aida Muhic and Kirsten Grunnet and Anders Ask and Costa, {Junia C} and Charlotte Kristiansen and Carsten Thomsen and Poulsen, {Hans Skovgaard} and Ulrik Lassen",
year = "2014",
month = "7",
doi = "10.3109/0284186X.2013.879607",
language = "English",
volume = "53",
pages = "939--44",
journal = "Acta Oncologica",
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publisher = "Taylor & Francis",
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Hofland, KF, Hansen, S, Sorensen, M, Engelholm, S, Schultz, HP, Muhic, A, Grunnet, K, Ask, A, Costa, JC, Kristiansen, C, Thomsen, C, Poulsen, HS & Lassen, U 2014, 'Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study', Acta Oncologica, bind 53, nr. 7, s. 939-44. https://doi.org/10.3109/0284186X.2013.879607

Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study. / Hofland, Kenneth F; Hansen, Steinbjørn; Sorensen, Morten; Engelholm, Silke; Schultz, Henrik P; Muhic, Aida; Grunnet, Kirsten; Ask, Anders; Costa, Junia C; Kristiansen, Charlotte; Thomsen, Carsten; Poulsen, Hans Skovgaard; Lassen, Ulrik.

I: Acta Oncologica, Bind 53, Nr. 7, 07.2014, s. 939-44.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme: A randomized phase II study

AU - Hofland, Kenneth F

AU - Hansen, Steinbjørn

AU - Sorensen, Morten

AU - Engelholm, Silke

AU - Schultz, Henrik P

AU - Muhic, Aida

AU - Grunnet, Kirsten

AU - Ask, Anders

AU - Costa, Junia C

AU - Kristiansen, Charlotte

AU - Thomsen, Carsten

AU - Poulsen, Hans Skovgaard

AU - Lassen, Ulrik

PY - 2014/7

Y1 - 2014/7

N2 - BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM.MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity.RESULTS: The response rate was 32% (95% CI 17-51%) for Bev-Tem (n = 32) and 23% (95% CI 9-44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable.CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

AB - BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM.MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide was given for five days every four weeks before and after radiotherapy and once daily during radiotherapy. The primary endpoint was response after neoadjuvant chemotherapy and a pre-specified response rate of 30% or more was considered of interest for future studies. Secondary endpoints were progression-free survival (PFS) and toxicity.RESULTS: The response rate was 32% (95% CI 17-51%) for Bev-Tem (n = 32) and 23% (95% CI 9-44%) for Bev-Iri (n = 31) (p = 0.56). Median PFS was 7.7 and 7.3 months for Bev-Tem and Bev-Iri, respectively. Hematological toxicity was more frequent with Bev-Tem including one death from febrile neutropenia whereas non-hematological toxicity was manageable.CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS.

U2 - 10.3109/0284186X.2013.879607

DO - 10.3109/0284186X.2013.879607

M3 - Journal article

VL - 53

SP - 939

EP - 944

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

IS - 7

ER -