title: Predictors of early treatment discontinuation in patients enrolled on Phase I oncology trials.
abstract: OBJECTIVE
  Patients who do not complete one cycle of therapy on Phase I trials for reasons other than dose limiting toxicity (DLT) are considered inevaluable for toxicity and must be replaced.
  
  
  METHODS
  Individual records from patients enrolled to NCI-sponsored Phase I trials activated between 2000 and 2010 were used. Early discontinuation was defined as the failure to begin cycle 2 for reasons other than a DLT during cycle 1. A multinomial logistic regression with a 3-level nominal outcome (early discontinuation, DLT during cycle 1, and continuation to cycl1e 2) was used with continuation to cycle 2 serving as the reference category. The final model was used to create two risk scores. An independent external cohort was used to validate these models.
  
  
  RESULTS
  Data from 3079 patients on 127 Phase I trials were analyzed. ECOG performance status (1, ≥ 2, two-sided P = .0315 and P = .0007), creatinine clearance (<60 ml/min, P = .0455), alkaline phosphatase (>2.5xULN, P = .0026), AST (>ULN, P = .0076), hemoglobin (<10 g/dL, P < .0001), albumin (<3.5 g/dL, P < .0001), and platelets (<400x109/L, P = .0732) were predictors of early discontinuation. The c-index of the final model was 0.63.
  
  
  CONCLUSIONS
  Knowledge of risk factors for early treatment discontinuation in conjunction with clinical judgment can help guide Phase I patient selection.
authors: Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Cornell Medical College, New York, NY 10065, USA.
authors: David M
authors: DM
authors: Hyman
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Anne A
authors: AA
authors: Eaton
authors: Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Cornell Medical College, New York, NY 10065, USA.
authors: Mrinal M
authors: MM
authors: Gounder
authors: Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Erika G
authors: EG
authors: Pamer
authors: Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Jasmine
authors: J
authors: Pettiford
authors: Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Cornell Medical College, New York, NY 10065, USA.
authors: Richard D
authors: RD
authors: Carvajal
authors: The National Cancer Institute, Bethesda, MD 20892, USA.
authors: S Percy
authors: SP
authors: Ivy
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Cornell Medical College, New York, NY 10065, USA.
authors: Alexia
authors: A
authors: Iasonos
authors: Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.|Weill Cornell Medical College, New York, NY 10065, USA.
authors: David R
authors: DR
authors: Spriggs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018579:Patient Selection; D012307:Risk Factors; D055815:Young Adult
keywords: Phase I trials; drug development; early discontinuation