title: An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer.
abstract: OBJECTIVE
  The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist histrelin ([ImBzl]D-His6,Pro9-Net) in 15 patients with disseminated prostate cancer.
  
  
  METHODS
  The 2.6 cm. implant releasing 60 microg. histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months.
  
  
  RESULTS
  LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 microg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients.
  
  
  CONCLUSIONS
  A histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.
authors.affiliation: Department of Urology, Shaare Zedek Medical Center and Zer Laboratories, Jerusalem, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Chertin
authors.forename: I M
authors.initials: IM
authors.lastname: Spitz
authors.forename: T
authors.initials: T
authors.lastname: Lindenberg
authors.forename: N
authors.initials: N
authors.lastname: Algur
authors.forename: T
authors.initials: T
authors.lastname: Zer
authors.forename: P
authors.initials: P
authors.lastname: Kuzma
authors.forename: A J
authors.initials: AJ
authors.lastname: Young
authors.forename: R
authors.initials: R
authors.lastname: Catane
authors.forename: A
authors.initials: A
authors.lastname: Farkas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D004343:Drug Implants; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D004343:Drug Implants; D007987:Gonadotropin-Releasing Hormone; C029256:histrelin