title: Nomogram to predict cycle-one serious drug-related toxicity in phase I oncology trials.
abstract: OBJECTIVE
  All patients in phase I trials do not have equivalent susceptibility to serious drug-related toxicity (SDRT). Our goal was to develop a nomogram to predict the risk of cycle-one SDRT to better select appropriate patients for phase I trials.
  
  
  METHODS
  The prospectively maintained database of patients with solid tumor enrolled onto Cancer Therapeutics Evaluation Program-sponsored phase I trials activated between 2000 and 2010 was used. SDRT was defined as a grade ≥ 4 hematologic or grade ≥ 3 nonhematologic toxicity attributed, at least possibly, to study drug(s). Logistic regression was used to test the association of candidate factors to cycle-one SDRT. A final model, or nomogram, was chosen based on both clinical and statistical significance and validated internally using a bootstrapping technique and externally in an independent data set.
  
  
  RESULTS
  Data from 3,104 patients enrolled onto 127 trials were analyzed to build the nomogram. In a model with multiple covariates, Eastern Cooperative Oncology Group performance status, WBC count, creatinine clearance, albumin, AST, number of study drugs, biologic study drug (yes v no), and dose (relative to maximum administered) were significant predictors of cycle-one SDRT. All significant factors except dose were included in the final nomogram. The model was validated both internally (bootstrap-adjusted concordance index, 0.60) and externally (concordance index, 0.64).
  
  
  CONCLUSIONS
  This nomogram can be used to accurately predict a patient's risk for SDRT at the time of enrollment. Excluding patients at high risk for SDRT should improve the safety and efficiency of phase I trials.
authors.affiliation: David M. Hyman, Anne A. Eaton, Mrinal M. Gounder, Erika G. Pamer, Martee L. Hensley, David R. Spriggs, and Alexia Iasonos, Memorial Sloan-Kettering Cancer Center; David M. Hyman, Mrinal M. Gounder, Martee L. Hensley, David R. Spriggs, and Alexia Iasonos, Weill Cornell Medical College, New York, NY; and Gary L. Smith and Percy Ivy, National Cancer Institute, Bethesda, MD.
authors.forename: David M
authors.initials: DM
authors.lastname: Hyman
authors.forename: Anne A
authors.initials: AA
authors.lastname: Eaton
authors.forename: Mrinal M
authors.initials: MM
authors.lastname: Gounder
authors.forename: Gary L
authors.initials: GL
authors.lastname: Smith
authors.forename: Erika G
authors.initials: EG
authors.lastname: Pamer
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.forename: David R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D015331:Cohort Studies; D016208:Databases, Factual; D006801:Humans; D008875:Middle Aged; D049451:Nomograms; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents