Neoadjuvant Bevacizumab and Irinotecan Versus Bevacizumab and Temozolomide Followed by Concomitant Chemoradiotherapy in Newly Diagnosed Glioblastoma Multiforme: A Randomized Phase II Study

Acta Oncol. 2014 Jul;53(7):939-44. doi: 10.3109/0284186X.2013.879607. Epub 2014 Jan 23.

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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / radiotherapy*
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Temozolomide
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Irinotecan
  • Dacarbazine
  • Camptothecin
  • Temozolomide