Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: results of a phase I/II double-blinded, randomized study.
OBJECTIVE
To evaluate the safety and activity of 6 months of treatment with lenalidomide at 5 or 25 mg/d in nonmetastatic biochemically relapsed prostate cancer.


METHODS
Sixty men with non-castrate, nonmetastatic, biochemically relapsed prostate cancer were stratified by prostate-specific antigen (PSA) doubling time, surgery/radiation therapy, prior androgen deprivation therapy (ADT), and randomized to lenalidomide 5 mg (n = 26) or 25 mg/d (n = 34) for 3 weeks repeated monthly for 6 months or until dose-limiting toxicity or disease progression. Toxicity was evaluated monthly, and PSAs and X-rays/scans every 6 months. Study size was determined to detect a progression rate of 40% at 6 months in either arm with 85% power (compared with a rate of 80% in the population receiving no treatment). Changes in PSA slopes were calculated using the regression of the log PSA for each patient before and during the initial 6 months and compared by t test.


RESULTS
Baseline variables were balanced between arms. Grade 3/4 toxicity rates were 12% (n = 3) with 5 mg and 29% (n = 10) with 25 mg (P = 0.1), most commonly neutropenia (five patients, all on 25 mg). Two patients per arm had thromboembolic events. The change in PSA slope was greater with 25 mg versus 5 mg [-0.172 (-0.24 to -0.11) versus -0.033 (-0.11 to 0.04); P = 0.005]. With a mean follow-up of 31.4 months (range 14-44), five patients on 25 mg and one patient on 5 mg remain on the study.


CONCLUSIONS
Lenalidomide has acceptable toxicity and is associated with long-term disease stabilization and PSA declines. Randomized studies evaluating conventional clinical disease end points in this patient population are planned.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. danielkeizman@gmail.com
Daniel
D
Keizman
Marianna
M
Zahurak
Victoria
V
Sinibaldi
Michael
M
Carducci
Samuel
S
Denmeade
Charles
C
Drake
Roberto
R
Pili
Emmanuel S
ES
Antonarakis
Susan
S
Hudock
Mario
M
Eisenberger
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012008:Recurrence; D013739:Testosterone / Q000032:analysis / Q000097:blood; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D013739:Testosterone; D013792:Thalidomide; D017430:Prostate-Specific Antigen; D000077269:Lenalidomide