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Clinical Impact of Adjuvant Chemotherapy in Glioblastoma Multiforme

A Meta-Analysis

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Abstract

Background: A meta-analysis of chemotherapy for glioblastoma multiforme (GBM) was performed. We sought to update prior analyses by focusing exclusively on GBM, including new trials of novel treatments, assessing effectiveness of individual treatment categories and presenting data in a clinically useful format.

Methods: A search of MEDLINE and EMBASE was conducted for randomised controlled trials of chemotherapy in GBM.

Results: Relative risks (RRs) for survival in 16 trials comparing chemotherapy with no chemotherapy were 1.18 (95% CI 1.08, 1.30) at 6 months, 1.53 (95% CI 1.26, 1.86) at 12 months and 2.12 (95% CI 1.60, 2.80) at 24 months. Nitrosourea compounds, local therapy (e.g. carmustine [1,3-bis [2-chloroethyl]-1-nitrosourea] wafers) and temozolomide were all more effective than no chemotherapy. Absolute increases in survival at 6, 12 and 24 months were 11%, 8% and 1%, respectively, for nitrosourea compounds; 8%, 24% and 5%, respectively, for local therapy; and 4%, 15% and 17%, respectively, for temozolomide. Efficacy of local therapy and temozolomide peaked at 12 and 18 months, respectively. After 2 years, nitrosourea compounds no longer provided clinically relevant benefit (number needed-to-treat [NNT] = 100; effect size [ES] = 0.17 SD), local therapy had diminishing returns (NNT = 20) that remained clinically relevant (ES = 0.71 SD) and temozolomide continued to show good efficacy (NNT = 5.9; ES = 0.74 SD). Survival was not significantly improved with multi-agent versus single-agent nitrosourea-based therapy in five trials: 6-month RR 0.91 (95% CI 0.71, 1.16); 24-month RR 1.33 (95% CI 0.72, 2.46).

Conclusion: Although nitrosourea compounds, local therapy and temozolomide are all effective in the treatment of GBM, local therapy and temozolomide may be associated with greater response, with clinically significant benefits extending to 24 months. The timing of peak benefits of local and temozolomide therapy suggests this combination may be more effective than single-agent chemotherapy and warrants further study.

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Acknowledgements

Dr Spiegel is supported by VA HSR&D Research Career Development Award RCD 03-179-2. Dr Esrailian is supported by NIH Training Grant T32 DK07180-30. Drs Spiegel and Esrailian are supported by the CURE Digestive Diseases Research Center (NIH 2P30 DK 041301-17).

This investigator-initiated study received funding from MGI Pharma (Baltimore, MD, USA). MGI Pharma manufactures carmustine wafers (Gliadel®), which is one of the therapies included in this analysis. Three authors (Brennan Spiegel, Eric Esrailian and Marc Chamberlain), two of whom (Brennan Spiegel and Eric Esrailian) performed the literature search, data abstraction and analyses and (with Marc Chamberlain) wrote the initial draft of the manuscript, were unaware of this funding source until the manuscript was completed. One author (Loren Laine) was aware of the funding source. Although he did have involvement in defining the aim of the study, designing the search strategy and manuscript preparation, he did not perform the data abstraction or statistical analyses. No funding source was involved in the literature search, data abstraction, data analysis, data synthesis or manuscript preparation.

Dr Chamberlain has received speakers bureau honoraria from MGI Pharma, Enzon, Chiron and Schering-Plough. Dr Laine has acted as a consultant to MGI Pharma. The authors have no other conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. VA Greater Los Angeles Healthcare System, Los Angeles, California, USA

    Brennan M. R. Spiegel

  2. David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, UCLA/VA Center for Outcomes Research and Education (C.O.R.E.), 11301 Wilshire Blvd, Building 115, Room 215, Los Angeles, California, 90073, USA

    Brennan M. R. Spiegel & Eric Esrailian

  3. UCLA/VA Center for Outcomes Research and Education, Los Angeles, California, USA

    Brennan M. R. Spiegel & Eric Esrailian

  4. Keck School of Medicine, University of Southern California, Los Angeles, California, USA

    Loren Laine

  5. University of South Florida, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA

    Marc C. Chamberlain

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  1. Brennan M. R. Spiegel
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Correspondence to Brennan M. R. Spiegel.

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Spiegel, B.M.R., Esrailian, E., Laine, L. et al. Clinical Impact of Adjuvant Chemotherapy in Glioblastoma Multiforme. CNS Drugs 21, 775–787 (2007). https://doi.org/10.2165/00023210-200721090-00006

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