Kinetics of serum androgen normalization and factors associated with testosterone reserve after limited androgen deprivation therapy for nonmetastatic prostate cancer.
OBJECTIVE
Groups have investigated time to testosterone recovery in patients who have undergone androgen deprivation therapy, usually by measuring androgen every 3 months, with varying results. To our knowledge this represents the largest study using monthly testosterone and dihydroxytestosterone measurement to evaluate the kinetics of androgen recovery following limited androgen deprivation therapy.


METHODS
Monthly serum androgen levels were analyzed following 2, 6-month cycles of gonadotropin-releasing hormone agonist therapy as part of a randomized, placebo controlled study of the role of thalidomide in delaying time to prostate specific androgen progression.


RESULTS
By the Kaplan-Meier method the median time to testosterone normalization in cycles 1 vs 2 was 15.4 vs 18.3 weeks with similar dihydroxytestosterone recovery times. Neither on-study prostate specific antigen, Gleason score nor thalidomide treatment had a significant impact on time to testosterone normalization. However, in cycle 1 men with low baseline dihydroxytestosterone and those who were more than 67 years old had significantly longer time to T normalization on Cox model analysis. Additionally, in cycle 2 patients with prior local radiation therapy had longer time to testosterone normalization, although this was no longer significant on Cox model analysis. Cox model analysis in cycle 2 showed that low baseline dihydroxytestosterone and testosterone, low testosterone nadir and white race were associated with longer time to testosterone normalization.


CONCLUSIONS
Findings of delayed testosterone recovery may be useful for designing and analyzing clinical trials of limited androgen deprivation therapy and for estimating the duration of treatment associated side effects in patients undergoing limited androgen deprivation therapy.
Gulley
James L
JL
Center for Cancer Research, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. gulleyj@mail.nih.gov
Aragon-Ching
Jeanny B
JB
Steinberg
Seth M
SM
Hussain
Maha H
MH
Sartor
Oliver
O
Higano
Celestia S
CS
Petrylak
Daniel P
DP
Chatta
Gurkamal S
GS
Arlen
Philip M
PM
Figg
William D
WD
Dahut
William L
WL
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000097:blood* / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001707:Biopsy, Needle; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D020127:Recovery of Function; D012016:Reference Values; D018570:Risk Assessment; D013739:Testosterone / Q000097:blood* / Q000378:metabolism; D013792:Thalidomide / Q000627:therapeutic use; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D013739:Testosterone; D013792:Thalidomide; D017430:Prostate-Specific Antigen; D016729:Leuprolide