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 cycle 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.