title: Temporal evolution of patient characteristics enrolled on phase I trials.
abstract: OBJECTIVE
  Phase I trials serve a crucial role in anticancer drug development. Given the explosion in the number of both approved anticancer therapies and agents in development, we hypothesized that the characteristics of patients enrolling on phase I clinical trials is evolving.
  
  
  METHODS
  We reviewed 476 published phase I trials over the past decade encompassing 15,100 patients and determined the following characteristics for patients enrolled: age; percentage with ECOG PS of 0, 1, or 2; sex; race; and number of prior chemotherapeutic therapies received: 0, 1, 2 or ≥ 3. We also identified the major tumor types enrolled: colorectal, lung, renal, breast, head/neck or "other". The change of patient characteristics over time as well as between the first half of studied period (period 1 = 1998-2001) and the second half period (period 2 = 2002-2006) was analyzed.
  
  
  RESULTS
  Colorectal and lung cancer patients together comprise ~35% of all patients enrolled on phase I trials and this has not changed over the past decade. The contribution of "other" malignancies has however significantly increased over time. The proportion of patients with PS2 has declined while that of PS1 has increased. The proportion of patients with ≥3 prior therapies prior to study enrollment has also significantly increased.
  
  
  CONCLUSIONS
  The shifting of patient characteristics especially as related to tumor types enrolled and number of prior therapies has important implications for future design of studies and inadequate attention to these issues may slow the accrual process.
authors.affiliation: Division of Hematology/Oncology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. afshin.dowlati@case.edu
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Madappa
authors.initials: M
authors.lastname: Kundranda
authors.forename: Sudhir
authors.initials: S
authors.lastname: Manda
authors.forename: Lauren
authors.initials: L
authors.lastname: Patrick
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D018579:Patient Selection; D013997:Time Factors