Phase I study of lenalidomide in solid tumors.
BACKGROUND
The primary objectives of this phase I study were to define a tolerable dose and to describe the toxicity of lenalidomide administered as a daily oral dose for 4 weeks followed by a 2-week rest period (6-week cycle) in patients with solid tumors that were refractory to standard treatment. The secondary objective was to document any antitumor activity.


METHODS
Key eligibility criteria included a performance status of 0-2 and acceptable hematologic, hepatic, and renal function. The dose was escalated from 5 to 10 to 25 mg/day. Nine cycles (54 weeks) were planned unless the patient developed intolerable toxicity or experienced tumor progression. Dose-limiting toxicity was defined as nonhematologic toxicity of grade 3 or higher and hematologic toxicity of grade 4 or higher occurring in cycle 1.


RESULTS
Overall, 20 patients were enrolled. One patient was ineligible due to a thromboembolic event within the preceding 6 months, but this was not known at enrollment and this patient was included in the analysis. Three, five, and 12 patients were treated with 5, 10, and 25 mg/day, respectively. One patient on 25 mg/day developed grade 3 motor neuropathy in cycle 1, and this was the only dose-limiting toxicity. Moderate dose-dependent and reversible hematologic toxicity was observed. The nonhematologic toxicities were otherwise mild to moderate over multiple cycles of lenalidomide. One patient had a partial response, and three patients had stable disease; three of these patients had non-small cell lung cancer.


CONCLUSIONS
The recommended dose of lenalidomide for further studies in patients with solid tumors is 25 mg/day for 4 weeks followed by a 2-week rest period.
Miller
Antonius A
AA
Wake Forest University, Comprehensive Cancer Center, Winston-Salem, NC 27157, USA. aamiller@wfubmc.edu
Case
Doug
D
Harmon
Michele
M
Savage
Paul
P
Lesser
Glenn
G
Hurd
David
D
Melin
Susan A
SA
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide