title: PRognostic factor of Early Death In phase II Trials or the end of 'sufficient life expectancy' as an inclusion criterion? (PREDIT model).
abstract: Optimizing patient selection is a necessary step to design better clinical trials. 'Life expectancy' is a frequent inclusion criterion in phase II trial protocols, a measure that is subjective and often difficult to estimate. The aim of this study was to identify factors associated with early death in patients included in phase II studies.
  
  
  
  We retrospectively collected medical records of patients with advanced solid tumors included in phase II trials in two French Comprehensive Cancer Centers (Bordeaux, Center 1 set; Lille, Center 2 set). We analyzed patients' baseline characteristics. Predictive factors associated with early death (mortality at 3 months) were identified by logistic regression. We built a model (PREDIT, PRognostic factor of Early Death In phase II Trials) based on prognostic factors isolated from the final multivariate model.
  
  
  
  Center 1 and 2 sets included 303 and 227 patients, respectively. Patients from Center 1 and 2 sets differed in tumor site, urological (26 % vs 15 %) and gastrointestinal (18 % vs 28 %) and in lung metastasis incidence (10 % vs 49 %). Overall survival (OS) at 3 months was 88 % (95 % CI [83.5; 91.0], Center 1 set) and 91 % (95 % CI [86.7; 94.2], Center 2 set). Presence of a 'life expectancy' inclusion criterion did not improve the 3-month OS (HR 0.6, 95 % CI [0.2; 1.2], p = 0.2325). Independent factors of early death were an ECOG score of 2 (OR 13.3, 95%CI [4.1; 43.4]), hyperleukocytosis (OR 5.5, 95 % CI [1.9; 16.3]) and anemia (OR 2.8, 95 % CI [1.1; 7.1]). Same predictive factors but with different association levels were found in the Center 2 set. Using the Center 1 set, ROC analysis shows a good discrimination to predict early death (AUC: 0.89 at 3 months and 0.86 at 6 months).
  
  
  
  Risk modeling in two independent cancer populations based on simple clinical parameters showed that baseline ECOG of 2, hyperleukocytosis and anemia are strong early-death predictive factors. This model allows identifying patients who may not benefit from a phase II trial investigational drug and may, therefore, represent a helpful tool to select patients for phase II trial entry.
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Centre Bordeaux, 229 cours de l'Argonne, 33076, Bordeaux, France.|University of Bordeaux, Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grellety
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Centre Bordeaux, 229 cours de l'Argonne, 33076, Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cousin
authors.affiliation: University of Bordeaux, Bordeaux, France.|Clinical and Epidemiological Research Unit Institut Bergonié, Bordeaux, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Letinier
authors.affiliation: University of Bordeaux, Bordeaux, France.|Clinical and Epidemiological Research Unit Institut Bergonié, Bordeaux, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Bosco-Lévy
authors.affiliation: Clinical and Epidemiological Research Unit Institut Bergonié, Bordeaux, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hoppe
authors.affiliation: University of Bordeaux, Bordeaux, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Joly
authors.affiliation: General Oncology Department, Centre Oscar Lambret, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.affiliation: University of Bordeaux, Bordeaux, France.|Clinical and Epidemiological Research Unit Institut Bergonié, Bordeaux, France.|INSERM, CIC1401 Epidemiological unit, Institut Bergonié, Bordeaux, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Mathoulin-Pelissier
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Centre Bordeaux, 229 cours de l'Argonne, 33076, Bordeaux, France. A.Italiano@bordeaux.unicancer.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
mesh_terms: D000328:Adult; D000368:Aged; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000401:mortality*; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000401:mortality* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009026:Mortality; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000401:mortality*
keywords: Drug trials; Early death; Phase II trial; Prognostic factors; “life expectancy” criterion