A new extra long acting depot preparation of the LHRH analogue Zoladex. First endocrinological and pharmacokinetic data in patients with advanced prostate cancer.
A new depot formulation of the LHRH analogue Zoladex (goserelin acetate) has been developed which releases the drug over a period of at least 3 months as judged by measurement of drug content in depots at intervals after insertion in male rats and by the suppression of oestrogen secretion and oestrus in female rats. This formulation is based on the lactide/glycolide polymer system used for the standard 1-month Zoladex depot, but the dose has been increased to 10.8 mg and the characteristics have been modified to enable a longer release of drug to be achieved. Thirty-eight patients with histologically proven, locally advanced (stage T3 or T4) and/or metastatic prostate cancer were treated with this new longer acting LHRH analogue depot formulation containing 10.8 mg Zoladex. After initial increase of serum testosterone in the first week of therapy, castration levels were reached in all patients after 4 weeks and this was maintained for more than 14 weeks. At the time of depot exhaustion, when escape from castration levels of androgen occurred, all patients received a single injection of a standard 1-month depot containing 3.6 mg Zoladex which restored castration levels of androgen thus showing that the pituitary gland was again suppressed. The tolerance and acceptability of the longer-acting depot is high and comparable to the 1-month depot. Taking into account social and psychological factors, patients with advanced prostate carcinoma will soon be able to be treated with a longer acting LHRH depot formulation every 3 months an alternative of the 1-month depot now widely used clinically.
Dijkman
G A
GA
Department of Urology, St Ignatius Hospital, Breda, The Netherlands.
del Moral
P F
PF
Plasman
J W
JW
Kums
J J
JJ
Delaere
K P
KP
Debruyne
F M
FM
Hutchinson
F J
FJ
Furr
B J
BJ
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002064:Buserelin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004361:Drug Tolerance; D017273:Goserelin; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013739:Testosterone / Q000097:blood*
D000970:Antineoplastic Agents; D017273:Goserelin; D013739:Testosterone; D007986:Luteinizing Hormone; D002064:Buserelin