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Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients

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Abstract

Even though past studies have suggested efficacy of nitrosourea drugs in patients with high-grade glioma and temozolomide has recently been shown significantly to be beneficial, no conclusive comparisons between these agents have been published. We performed a survival gain analysis of 364 studies describing 24,193 patients with high-grade glioma treated in 504 cohorts, and compared the effects of drugs. The most frequent diagnoses were glioblastoma multiforme (GBM) (72%) and anaplastic astrocytoma (22%). The mean overall survival (mOS) was 14.1 months. The outcome was influenced by several of the known prognostic factors including the histological grade, if the tumors were newly diagnosed or recurrent, the completeness of resection, patients’ age, and gender. This information allowed the calculation of a predicted mOS for each cohort based on their prognostic factors independent of treatment. Survival gain to characterize the influence of treatment was subsequently defined and validated as the difference between the observed and the predicted mOS. In 62 CCNU-treated cohorts and 15 ACNU-treated cohorts the survival gain was 5.3 months and 8.9 months (P < 0.0005), respectively. No detectable survival gain for patients treated with various BCNU-containing regimens was found. Conclusion CCNU- and ACNU- containing regimens were superior to BCNU containing regiments.

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Abbreviations

ACNU:

Nimustine

BCNU:

Carmustine

CCNU:

Lomustine

MCNU:

Ranimustine

PCNU:

1-(2-Chloroethyl)-3-(2,6-dioxo-3-piperidyl)

GBM:

Glioblastoma multiforme

LC50 :

Lethal concentration resulting in killing of 50% of cells

mOS:

Median overall survival

MW:

Molecular weight

SG:

Survival gain

SPSS:

Statistical package for social studies

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Acknowledgement

We thank Holger Hauch M.D, and Benjamin Nebiyou Bekele Ph.D. for helpful discussions. The work was supported by the NIH core grant CA16672.

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Authors and Affiliations

  1. Children’s Cancer Hospital, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Johannes E. A. Wolff

  2. Department of Pediatric Hematology-Oncology, Marmara University Medical Center, Altunizade, Istanbul, Turkey

    Su Berrak

  3. Department of Pharmacy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Susannah E. Koontz Webb

  4. Department of Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Ming Zhang

Authors
  1. Johannes E. A. Wolff
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  2. Su Berrak
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  3. Susannah E. Koontz Webb
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  4. Ming Zhang
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Correspondence to Johannes E. A. Wolff.

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Wolff, J.E.A., Berrak, S., Koontz Webb, S.E. et al. Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients. J Neurooncol 88, 57–63 (2008). https://doi.org/10.1007/s11060-008-9533-5

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  • DOI: https://doi.org/10.1007/s11060-008-9533-5

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