Nomogram to predict cycle-one serious drug-related toxicity in phase I oncology trials Journal Article


Authors: Hyman, D. M.; Eaton, A. A.; Gounder, M. M.; Smith, G. L.; Pamer, E. G.; Hensley, M. L.; Spriggs, D. R.; Ivy, P.; Iasonos, A.
Article Title: Nomogram to predict cycle-one serious drug-related toxicity in phase I oncology trials
Abstract: 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. 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. 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). 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.
Keywords: adolescent; adult; treatment outcome; aged; aged, 80 and over; middle aged; young adult; antineoplastic agents; methodology; antineoplastic agent; prospective study; prospective studies; cohort studies; statistics; cohort analysis; risk factors; risk factor; nomograms; multicenter study; clinical trials, phase i as topic; factual database; databases, factual; nomogram; phase 1 clinical trial (topic); very elderly; humans; prognosis; human; article
Journal Title: Journal of Clinical Oncology
Volume: 32
Issue: 6
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2014-02-20
Start Page: 519
End Page: 526
Language: English
DOI: 10.1200/jco.2013.49.8808
PUBMED: 24419130
PROVIDER: scopus
PMCID: PMC3918535
DOI/URL:
Notes: Export Date: 1 May 2014 -- Source: Scopus
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MSK Authors
  1. Alexia Elia Iasonos
    169 Iasonos
  2. Martee L Hensley
    211 Hensley
  3. Mrinal M Gounder
    65 Gounder
  4. David Hyman
    176 Hyman
  5. Anne Austin Eaton
    112 Eaton
  6. David R Spriggs
    302 Spriggs
  7. Erika   Pamer
    7 Pamer