Predictors of early treatment discontinuation in patients enrolled on Phase I oncology trials.

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.

Increases in impulsivity following smoking abstinence are related to baseline nicotine intake and boredom susceptibility.

Trait impulsivity and response inhibition have been shown to be related to smoking behavior. One measure of response inhibition - antisaccade performance, or the ability to inhibit looking at a novel stimulus - has been shown to be worsened by smoking abstinence, improved by nicotine administration and predictive of smoking cessation outcomes. However, relations between antisaccade performance and measures of trait impulsivity have not been extensively evaluated in smokers. In the present study, twelve dependent smokers (n=12) completed an eye tracking task following smoking as usual and overnight abstinence; and they completed baseline measures of trait impulsivity, smoking history and provided biological samples. As expected, overnight abstinence significantly increased antisaccade errors (p<0.002) while having no effect on prosaccade performance. Abstinence-induced increases in antisaccade errors were positively correlated with baseline plasma cotinine and Sensation Seeking Scale Boredom Susceptibility, and negatively correlated with IQ. These results suggest that smoking abstinence significantly increases errors of response inhibition and that the magnitude of this increase is related to trait impulsivity and nicotine intake variables.