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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