Rapid androgen cycling as treatment for patients with prostate cancer.
OBJECTIVE
To investigate the safety and feasibility of rapid androgen cycling for men with progressive prostate cancer.


METHODS
Schedule 1 included a 4-week induction of androgen depletion, followed by 4-week treatment cycles of a monthly gonadotropin-releasing hormone agonist, testosterone on days 1 to 7, and an estrogen patch on days 8 to 21. Schedule 2 included a 12-week induction of androgen depletion followed by 4-week cycles of gonadotropin-releasing hormone agonist and testosterone, but no estrogens for patients with a prostate-specific antigen (PSA) nadir <1 ng/mL after induction. The primary end point was serially declining PSA trough values over six treatment cycles.


RESULTS
Thirty-six patients were treated; 27 were evaluable after cycling, of whom 8 of 12 (67%) and 9 of 15 (60%) on schedules 1 and 2, respectively, reached the end point. Five patients with PSA >1 ng/mL following induction did not cycle. No patient progressed radiographically or clinically during cycling. Three posttherapy PSA patterns were observed: a decline followed by a rapid increase in trough levels, a sustained decline with a plateau at a detectable nadir, and a decline to an undetectable nadir. Mean testosterone levels were castrate at the time of trough and in the normal physiologic range following androgen repletion. Major toxicities included grades 1 and 2 fatigue, hepatitis, gynecomastia, and hot flashes.


CONCLUSIONS
Rapid hormonal cycling is feasible and well tolerated, and successive declines in PSA troughs are achievable. Although the sample size was small, the proportion of patients achieving declining PSA at the end of six cycles was comparable with that reached with continuous androgen depletion therapy.
Feltquate
David
D
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nordquist
Luke
L
Eicher
Caitlin
C
Morris
Michael
M
Smaletz
Oren
O
Slovin
Susan
S
Curley
Tracy
T
Wilton
Andrew
A
Fleisher
Martin
M
Heller
Glenn
G
Scher
Howard I
HI
D000368:Aged; D000728:Androgens / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage*; D005240:Feasibility Studies; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000819:agonists / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood
D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D017430:Prostate-Specific Antigen