title: Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas.
abstract: The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials.
authors: Department of Neurological Surgery, University of California-San Francisco, 400 Parnassus Avenue, UC Clinics 808, San Francisco, CA 94143-0372, USA. lambornk@neurosurg.ucsf.edu
authors: Kathleen R
authors: KR
authors: Lamborn
authors: W K Alfred
authors: WK
authors: Yung
authors: Susan M
authors: SM
authors: Chang
authors: Patrick Y
authors: PY
authors: Wen
authors: Timothy F
authors: TF
authors: Cloughesy
authors: Lisa M
authors: LM
authors: DeAngelis
authors: H Ian
authors: HI
authors: Robins
authors: Frank S
authors: FS
authors: Lieberman
authors: Howard A
authors: HA
authors: Fine
authors: Karen L
authors: KL
authors: Fink
authors: Larry
authors: L
authors: Junck
authors: Lauren
authors: L
authors: Abrey
authors: Mark R
authors: MR
authors: Gilbert
authors: Minesh
authors: M
authors: Mehta
authors: John G
authors: JG
authors: Kuhn
authors: Kenneth D
authors: KD
authors: Aldape
authors: Janelle
authors: J
authors: Hibberts
authors: Pamela M
authors: PM
authors: Peterson
authors: Michael D
authors: MD
authors: Prados
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents