Predictors of early treatment discontinuation in patients enrolled on Phase I oncology trials. Academic Article uri icon

Overview

abstract

  • PURPOSE: 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. CONCLUSION: Knowledge of risk factors for early treatment discontinuation in conjunction with clinical judgment can help guide Phase I patient selection.

publication date

  • August 7, 2015

Research

keywords

  • Clinical Trials, Phase I as Topic

Identity

PubMed Central ID

  • PMC4662493

Scopus Document Identifier

  • 84938845910

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.2909

PubMed ID

  • 25682870

Additional Document Info

volume

  • 6

issue

  • 22