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

  • Johannes E. A. Wolff
  • Su Berrak
  • Susannah E. Koontz Webb
  • Ming Zhang
Clinical-patient Studies

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.

Keywords

Nimustine Carmustine Lomustine Ranimustine 1-(2-Chloroethyl)-3-(2,6-dioxo-3-piperidyl) Glioblastoma multiforme Survival gain 

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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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Johannes E. A. Wolff
    • 1
  • Su Berrak
    • 2
  • Susannah E. Koontz Webb
    • 3
  • Ming Zhang
    • 4
  1. 1.Children’s Cancer Hospital, Unit 87The University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Pediatric Hematology-OncologyMarmara University Medical CenterAltunizadeTurkey
  3. 3.Department of PharmacyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  4. 4.Department of Biostatistics and Applied MathematicsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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