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

David M. Hyman, Anne A. Eaton, Mrinal M. Gounder, Erika G. Pamer, Jasmine Pettiford, Richard D. Carvajal, S. Percy Ivy, Alexia Iasonos, David R. Spriggs

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)19316-19327
Number of pages12
Issue number22
StatePublished - 2015
Externally publishedYes


  • Drug development
  • Early discontinuation
  • Phase i trials

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