PURPOSE: Alterations in renal clearance of anticancer drugs can affect the occurrence of @entity137 related to drug exposure. The National @entity5 Institute and the US Food and Drug Administration (FDA) use different criteria to classify @entity8 . We examined those discrepancies and their potential association with the incidence of @entity137 in @entity1 enrolled onto @entity5 Therapy Evaluation Program-sponsored single-agent phase I studies over three decades (1979 to 2010). METHODS: Data to estimate @entity1011 clearance according to the Cockcroft-Gault and Jelliffe formulas were available from 10,236 @entity1 , and data to estimate @entity1011 clearance according to the six- and four-variable Modification of Diet in @entity8 formulas were available from a subset (n = 4,084). @entity1 were classified according to National @entity5 Institute and FDA criteria, and the rates of clinically relevant @entity137 were evaluated within groups and compared among groups. RESULTS: Cockcroft-Gault estimated renal function improved over time, which may be attributed to an increase in weight of @entity1 in the same time frame. Approximately 36% of @entity1 enrolled onto phase I trials had mild @entity8 by FDA criteria. Relative to normal function, mild @entity8 was associated with a statistically significant but small increase in grade 3 or 4 nonhematologic @entity137 and any relevant @entity137 . CONCLUSION: @entity1 with mild @entity8 by FDA criteria have routinely been enrolled onto phase I studies of antineoplastics without clinically meaningful increase in the risk of @entity137 . In future oncology @entity8 trials based on the FDA classification, the FDA mild group may only need to be activated when the moderate and normal groups differ substantially in tolerability or pharmacokinetics.

Effect of Renal Dysfunction on @entity137 in Three Decades of XXXX Therapy Evaluation Program-Sponsored Single-Agent Phase I Studies.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity8 :: ('MESH:D007674', 'Disease') :: ['Renal Disease', 'renal dysfunction'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity5 :: ('MESH:D009369', 'Disease') :: ['Cancer'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine']
@entity5 :: (MESH:D009369,Disease) :: ['Cancer']
