title: Systematic review and meta-analysis of phase I/II targeted therapy combined with radiotherapy in patients with glioblastoma multiforme: quality of report, toxicity, and survival.
abstract: To perform a systematic review and meta-analysis of severe adverse events (SAE) reported in early trials combining molecularly targeted therapies (MTT) with radiotherapy (RT), and to compare them to standard therapy. A summary data meta-analysis was performed and compared to the historical standard. Inclusion criteria were phase I and/or II trials published between 2000 and 2011, with glioblastoma multiforme patients treated with RT and MTT. Pooled incidence rates (IR) of SAE were estimated as well as the pooled median progression-free survival (PFS) and overall survival (OS). Nineteen prospective trials (9 phase I, 1 phase I/II and 9 phase II) out of 29 initially selected were included (n = 755 patients). The exact number of patients who had experienced SAE was mentioned in 37 % of the trials, concerning only 17 % of the patients. Information such as the period during which adverse events were monitored, the planned treatment duration, and late toxicity were not reported in the trials. The pooled IR of overall SAE was 131.2 (95 % CI 88.8-193.7) per 1000 person-months compared to 74.7 (63.6-87.8) for standard therapy (p < 0.01). Significant differences were observed for gastrointestinal events (p = 0.05) and treatment-related deaths (p = 0.02), in favour of standard therapy. No significant difference was observed in PFS and OS. Reporting a summary of toxicity data in early clinical trials should be stringently standardized. The use of MTT with RT compared to standard therapy increased SAE while yielded comparable survival in glioblastoma multiforme patients.
authors.affiliation: Department of Radiation Oncology, INSERM 1030 "Molecular Radiotherapy", Gustave Roussy, Gustave Roussy Cancer Campus, 114 Rue Édouard Vaillant, 94805, Villejuif Cedex, France.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: dos Santos
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.forename: Delphine
authors.initials: D
authors.lastname: Lefeuvre
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
authors.forename: Mehdi
authors.initials: M
authors.lastname: Touat
authors.forename: Guillaume
authors.initials: G
authors.lastname: Louvel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dhermain
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Eric
authors.initials: E
authors.lastname: Deutsch
authors.forename: Gwénaël
authors.initials: G
authors.lastname: Le Teuff
mesh_terms: D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000401:mortality*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000401:mortality*; D011379:Prognosis; D011787:Quality of Health Care; D011879:Radiotherapy Dosage; D015996:Survival Rate