title: Patient selection for oncology phase I trials: a multi-institutional study of prognostic factors.
abstract: OBJECTIVE
  The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials.
  
  
  METHODS
  Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis.
  
  
  RESULTS
  The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality.
  
  
  CONCLUSIONS
  Patient selection using any of these prognostic scores will reduce non-drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days.
authors.affiliation: The Royal Marsden National Health Service Foundation Trust, Sutton, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Olmos
authors.forename: Roger P
authors.initials: RP
authors.lastname: A'hern
authors.forename: Silvia
authors.initials: S
authors.lastname: Marsoni
authors.forename: Rafael
authors.initials: R
authors.lastname: Morales
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez-Roca
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.forename: Joo Ern
authors.initials: JE
authors.lastname: Ang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.forename: Jan H
authors.initials: JH
authors.lastname: Schellens
authors.forename: Gianluca
authors.initials: G
authors.lastname: Del Conte
authors.forename: Andre T
authors.initials: AT
authors.lastname: Brunetto
authors.forename: T R Jeffry
authors.initials: TR
authors.lastname: Evans
authors.forename: Richard
authors.initials: R
authors.lastname: Wilson
authors.forename: Elisa
authors.initials: E
authors.lastname: Gallerani
authors.forename: Ruth
authors.initials: R
authors.lastname: Plummer
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017321:Clinical Trials, Phase I as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D018579:Patient Selection; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D055815:Young Adult