Determining dosing intervals for luteinizing hormone releasing hormone agonists based on serum testosterone levels: a prospective study.
OBJECTIVE
Long acting luteinizing hormone releasing hormone agonists are the predominant form of androgen suppression in the treatment of prostate cancer with the goal of maintaining castrate levels of testosterone. Current dosing of luteinizing hormone releasing hormone agonists does not include monitoring the end organ response of serum testosterone. Recent evidence suggests standard dosing regimens fail to achieve castrate levels of testosterone in some patients while in other patients testosterone can remain at castrate levels longer than the manufacturer recommended dosing interval. We prospectively evaluated patients with prostate cancer receiving luteinizing hormone releasing hormone agonist hormonal therapy to determine the length of time that serum testosterone remains at or below castrate levels.


METHODS
A 3-month dose of 22.5 mg leuprolide was administered to all patients as a first dose followed by a second dose 3 months later. Serum testosterone and prostate specific antigen were measured prospectively before starting hormonal therapy, after the first dose (12 weeks) and again following the second dose (24 weeks) to assess if castrate levels of testosterone (50 ng/dl or less) had been reached. At 24 weeks if patient serum testosterone was 50 ng/dl or less, then 22.5 mg leuprolide were not administered, and serum testosterone and prostate specific antigen were checked monthly. When serum testosterone was greater than 50 ng/dl a subsequent dose of 22.5 mg leuprolide was given. Serum testosterone and prostate specific antigen were then checked 3 months later and monthly thereafter until testosterone was greater than 50 ng/dl. Thus, the time that testosterone remained at castrate levels could be accurately established.


RESULTS
From February 2003 to August 2005, 42 patients were treated in this manner with a median followup of 18 months (range 10 to 30). Average patient age was 77 years. Median Gleason grade was 7 (range 6 to 9). Median pretreatment prostate specific antigen was 15.1 ng/ml (range 0.6 to 433) and median posttreatment prostate specific antigen was 0.74 (less than 0.1 to 120). The median dosing interval was 6 months (range 5 to 12). Three patients had an increase in prostate specific antigen while receiving treatment despite castrate levels of testosterone. No patient required more frequent dosing than every 5 months.


CONCLUSIONS
Testosterone based luteinizing hormone releasing hormone agonist therapy makes empirical sense. It represents continuous androgen ablation based on the patient physiological end point, namely testosterone. Early data suggest that using serum testosterone to guide luteinizing hormone releasing hormone dosing is safe, efficacious and cost-effective. By following end organ response, patients receive individualized care and more accurate androgen suppression therapy.
Pathak
Apurba S
AS
Department of Urology, Kaiser Permanente Los Angeles, 4900 Sunset Boulevard, Los Angeles, CA 90027, USA. apurba.s.pathak@kp.org
Pacificar
Judy S
JS
Shapiro
Charles E
CE
Williams
Stephen G
SG
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood*; D013739:Testosterone / Q000097:blood*
D018931:Antineoplastic Agents, Hormonal; D013739:Testosterone; D017430:Prostate-Specific Antigen; D016729:Leuprolide