title: "Classical 3 + 3 design" versus "accelerated titration designs": analysis of 270 phase 1 trials investigating anti-cancer agents.
abstract: The number of patients treated at each dose-level in dose seeking phase I trials is arbitrarily established. The most frequently used design is the "classical 3 + 3 design (3 + 3D)". Recently, Simon et al. had introduced several "accelerated titration designs (ATD)". In the present analysis, we compared the performance of these two types of designs in 270 recently (1997-2008) published phase I trials. ATD had been used in only 10% of the recent studies. ATD had permitted to explore significantly more dose levels (seven versus five, p = 0.0001) and reduced the rate of patients treated at doses below phase-2 recommended dose (46% versus 56%, p = 0.0001). Nevertheless, ATD did not allow a reduction in the number of enrolled patients, shorten the accrual time nor increase the efficacy of phase I trials. These data support that ATD as an effective clinical trial design over a standard 3 + 3 dose escalation design.
authors.affiliation: Département de Cancérologie Générale, Centre Oscar Lambret, 3, Rue F Combemale, 59020, Lille, France. n-penel@o-lambret.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Isambert
authors.forename: Pierre
authors.initials: P
authors.lastname: Leblond
authors.forename: Charles
authors.initials: C
authors.lastname: Ferte
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonneterre
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents