Predictors of early treatment discontinuation in patients enrolled on Phase I oncology trials Journal Article
| Authors: | Hyman, D. M.; Eaton, A. A.; Gounder, M. M.; Pamer, E. G.; Pettiford, J.; Carvajal, R. D.; Percy Ivy, S.; Iasonos, A.; Spriggs, D. R. |
| Article Title: | Predictors of early treatment discontinuation in patients enrolled on Phase I oncology trials |
| 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 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. |
| Keywords: | adult; controlled study; aged; major clinical study; validation process; bone metastasis; cancer radiotherapy; lymph node metastasis; antineoplastic agent; diagnostic accuracy; prospective study; sensitivity and specificity; melanoma; controlled clinical trial; breast cancer; skin cancer; cohort analysis; drug development; urogenital tract cancer; risk factor; risk assessment; aspartate aminotransferase blood level; digestive system cancer; sarcoma; alkaline phosphatase; aspartate aminotransferase; liver metastasis; lung metastasis; albumin; head and neck cancer; multicenter study; medical record; brain metastasis; thrombocyte count; predictor variable; brain cancer; alkaline phosphatase blood level; phase 1 clinical trial; cancer classification; thorax tumor; treatment withdrawal; creatinine clearance; female genital tract cancer; phase i trials; human; male; female; article; early discontinuation |
| Journal Title: | Oncotarget |
| Volume: | 6 |
| Issue: | 22 |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Date Published: | 2015-08-07 |
| Start Page: | 19316 |
| End Page: | 19327 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 25682870 |
| PMCID: | PMC4662493 |
| DOI: | 10.18632/oncotarget.2909 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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