Intermittent androgen suppression in the LuCaP 23.12 prostate cancer xenograft model

• Published in: The Prostate Vol. 43; no. 1; pp. 63 - 70
• Main Authors: Buhler, Kent R., Santucci, Richard A., Royai, Ramin A., Whitney, Sarah C., Vessella, Robert L., Lange, Paul H., Ellis, William J.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.04.2000; Wiley-Liss
• Subjects: androgens; animal models; Animals; Biological and medical sciences; cancer cell progression; Drug Administration Schedule; Humans; Male; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Prostate-Specific Antigen - blood; prostatic neoplasms; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Random Allocation; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the genital tract and mammary gland; Testosterone - administration & dosage; Testosterone - therapeutic use; Transplantation, Heterologous; Animal model; Hormonodependence; Urinary system disease; Prostate disease; Androgen; Rodentia; Malignant tumor; Intermittency; Vertebrata; Mammalia; Treatment; Castration; Mouse; Animal; Surgery; Sex steroid hormone; Male genital diseases; Prostate
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/(SICI)1097-0045(20000401)43:1<63::AID-PROS9>3.0.CO;2-D

BACKGROUND Intermittent androgen suppression (IAS) has been proposed as a method of delaying the onset of androgen‐independent growth in prostate cancer. While several pilot studies have demonstrated the feasibility of such a treatment, no study to date has defined the effect of IAS on survival. METHODS We developed an IAS protocol for mice bearing the LuCaP 23.12 human prostate cancer xenograft, with each cycle consisting of 1 week of androgen replacement with a testosterone pellet followed by 3 weeks of androgen withdrawal. Mice that responded to castration with a 40% or greater decrease in serum prostate‐specific antigen (PSA) were randomized to treatment with either continuous androgen suppression (CAS) or IAS. Serum PSA, tumor volume, and overall survival were monitored. RESULTS A total of 75 mice met the randomization criteria. There was no significant difference of survival between animals treated with CAS or IAS (185 vs. 239 days, P = 0.1835). Serum PSA showed evidence of cycling with hormonal manipulation. No cycling was noted in tumor volume. CONCLUSIONS IAS is not associated with a decrease in survival compared to CAS, yet in patients may offer quality‐of‐life improvements. Further studies of IAS in the setting of Institutional Review Board (IRB) approved clinical trials should be encouraged. Prostate 43:63–70, 2000. Published 2000 Wiley‐Liss, Inc.