Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: Results of a phase I/II double-blinded, randomized study

Daniel Keizman, Marianna Zahurak, Victoria Sinibaldi, Michael Carducci, Samuel Denmeade, Charles Drake, Roberto Pili, Emmanuel S. Antonarakis, Susan Hudock, Mario Eisenberger

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)5269-5276
Number of pages8
JournalClinical Cancer Research
Volume16
Issue number21
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

Prostate-Specific Antigen
Prostatic Neoplasms
Neutropenia
Population
Androgens
Disease Progression
lenalidomide
Research Design
Radiotherapy
Therapeutics
X-Rays
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Keizman, D., Zahurak, M., Sinibaldi, V., Carducci, M., Denmeade, S., Drake, C., ... Eisenberger, M. (2010). Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: Results of a phase I/II double-blinded, randomized study. Clinical Cancer Research, 16(21), 5269-5276. https://doi.org/10.1158/1078-0432.CCR-10-1928

Lenalidomide in nonmetastatic biochemically relapsed prostate cancer : Results of a phase I/II double-blinded, randomized study. / Keizman, Daniel; Zahurak, Marianna; Sinibaldi, Victoria; Carducci, Michael; Denmeade, Samuel; Drake, Charles; Pili, Roberto; Antonarakis, Emmanuel S.; Hudock, Susan; Eisenberger, Mario.

In: Clinical Cancer Research, Vol. 16, No. 21, 01.11.2010, p. 5269-5276.

Research output: Contribution to journalArticle

Keizman, D, Zahurak, M, Sinibaldi, V, Carducci, M, Denmeade, S, Drake, C, Pili, R, Antonarakis, ES, Hudock, S & Eisenberger, M 2010, 'Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: Results of a phase I/II double-blinded, randomized study', Clinical Cancer Research, vol. 16, no. 21, pp. 5269-5276. https://doi.org/10.1158/1078-0432.CCR-10-1928
Keizman, Daniel ; Zahurak, Marianna ; Sinibaldi, Victoria ; Carducci, Michael ; Denmeade, Samuel ; Drake, Charles ; Pili, Roberto ; Antonarakis, Emmanuel S. ; Hudock, Susan ; Eisenberger, Mario. / Lenalidomide in nonmetastatic biochemically relapsed prostate cancer : Results of a phase I/II double-blinded, randomized study. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 21. pp. 5269-5276.
@article{2bd36a5451fd468089830189dae81238,
title = "Lenalidomide in nonmetastatic biochemically relapsed prostate cancer: Results of a phase I/II double-blinded, randomized study",
abstract = "Purpose: 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. Experimental Design: 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.",
author = "Daniel Keizman and Marianna Zahurak and Victoria Sinibaldi and Michael Carducci and Samuel Denmeade and Charles Drake and Roberto Pili and Antonarakis, {Emmanuel S.} and Susan Hudock and Mario Eisenberger",
year = "2010",
month = "11",
day = "1",
doi = "10.1158/1078-0432.CCR-10-1928",
language = "English (US)",
volume = "16",
pages = "5269--5276",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "21",

}

TY - JOUR

T1 - Lenalidomide in nonmetastatic biochemically relapsed prostate cancer

T2 - Results of a phase I/II double-blinded, randomized study

AU - Keizman, Daniel

AU - Zahurak, Marianna

AU - Sinibaldi, Victoria

AU - Carducci, Michael

AU - Denmeade, Samuel

AU - Drake, Charles

AU - Pili, Roberto

AU - Antonarakis, Emmanuel S.

AU - Hudock, Susan

AU - Eisenberger, Mario

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Purpose: 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. Experimental Design: 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.

AB - Purpose: 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. Experimental Design: 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.

UR - http://www.scopus.com/inward/record.url?scp=78049477140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78049477140&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-10-1928

DO - 10.1158/1078-0432.CCR-10-1928

M3 - Article

C2 - 20978144

AN - SCOPUS:78049477140

VL - 16

SP - 5269

EP - 5276

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 21

ER -