title: Do glioma patients derive any therapeutic benefit from taking a higher cumulative dose of temozolomide regimens?: a meta-analysis.
abstract: Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients.All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled.Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94-1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96-1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03-2.46, P = 0.04) among the HCD group.Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle.
authors.affiliation: From the Department of Radiation Oncology (HS, SD, GL, CR, YWY), Southern Medical University Nanfang Hospital; Department of Radiation Oncology, Shenzhen people's hospital,Second Clinical Medicine College of Jinan University (GL) and Department of Rehabilitation (XX), Southern Medical University Zhujiang Hospital, Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Shasha
authors.initials: S
authors.lastname: Du
authors.forename: Guixiang
authors.initials: G
authors.lastname: Liao
authors.forename: Xiao
authors.initials: X
authors.lastname: Xie
authors.forename: Chen
authors.initials: C
authors.lastname: Ren
authors.forename: Ya Wei
authors.initials: YW
authors.lastname: Yuan
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide