Inhibition of the pituitary-gonadal axis by a single intramuscular administration of D-Trp-6-LH-RH (decapeptyl) in a sustained-release formulation in patients with prostatic carcinoma.
For the past 6 years we used daily injection of luteinizing hormone-releasing hormone (LH-RH) agonists to treat patients with advanced prostate carcinoma. In this study we determined the hormonal response of the pituitary-testicular axis over a 2-month period and evaluated the safety and tolerance of the single intramuscular administration of sustained-release formulations of D-Trp-6-LH-RH microcapsules designed to release 50, 100, or 200 micrograms/day for over 1 month. Serum levels of LH, testosterone, and D-Trp-6-LH-RH were measured by RIA for up to 60 days in 10 patients with advanced prostatic carcinoma who had not received any previous drug therapy. After the administration of the microcapsules there was a biphasic increase in D-Trp-6-LH-RH serum levels. The maximal peak was obtained between 1 and 3 hr, and a second peak occurred between weeks 4 and 6. LH levels increased initially, with a maximal peak at 60 min, and elevated serum LH values persisted for more than 24 hr. LH levels began to fall on the second day, reaching subnormal values after 1 week. Serum testosterone rose during the first week and fell subsequently to less than 100 ng/dl. A rebound in LH and testosterone was seen about the 50th day after the microcapsule administration. Following the first week of therapy, we observed in all patients a significant decrease in bone pain, improvement in urinary flow obstruction, and a reversal of the signs of prostatism. No side effects were observed, and acceptance of the microcapsules was very good. Our results show that a single dose of D-Trp-6-LH-RH microcapsules suppresses of the pituitary-testicular axis for at least 50 days. D-Trp-6-LH-RH microcapsules facilitate the treatment and should lead to an improvement in the therapeutic response.
Gonzalez-Barcena
D
D
Hospital de Especialidades Centro Medico La Raza, Mexico City, Mexico.
Perez-Sanchez
P L
PL
Graef
A
A
Gomez
A M
AM
Berea
H
H
Comaru-Schally
A M
AM
Schally
A V
AV
D000135:Acid Phosphatase / Q000097:blood; D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood; D002214:Capsules; D003692:Delayed-Action Preparations; D004341:Drug Evaluation; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood; D017329:Triptorelin Pamoate
D000970:Antineoplastic Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D000135:Acid Phosphatase