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Phase I Study of Oral Lenalidomide in Patients With Refractory Metastatic Cancer
Author(s) -
Dahut William L.,
AragonChing Jeanny B.,
Woo Sukyung,
Tohnya Tanyifor M.,
Gulley James L.,
Arlen Philip M.,
Wright John J.,
Ventiz Jurgen,
Figg William D.
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009335001
Subject(s) - lenalidomide , medicine , neutropenia , pharmacokinetics , nausea , rash , refractory (planetary science) , dosing , cancer , gastroenterology , multiple myeloma , urology , chemotherapy , physics , astrobiology
Objectives of this study were to determine the maximum tolerated dose and to characterize the side effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n = 15), later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, with a 21 days‐on and 7 days‐off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range of doses with the mean half‐life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared with patients with normal function (CL/F = 243 mL/min). Stable disease was documented in 12 of 44 evaluable patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to a 35‐mg/d intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies.