3- Goserelin
Goserelin acetate (Zoladex, AstraZeneca) is an injectable
gonadotropin releasing hormone superagonist (GnRH agonist), also known as a
luteinizing hormone releasing hormone (LHRH) agonist. Structurally, it is a
decapeptide. Goserelin acetate is used to suppress production of the sex
hormones (testosterone and estrogen), particularly in the treatment of breast
and prostate cancer.
Goserelin acetate stimulates the production of the sex hormones
testosterone and estrogen in a non-pulsatile (non-physiological) manner. This
causes the disruption of the endogenous hormonal feedback systems, resulting in
the down-regulation of testosterone and estrogen production.
Zoladex was approved by the U.S. Food and Drug Administration in
1989 for treatment of prostate cancer.
Pharmacokinetics
Goserelin is a synthetic analogue of a naturally occurring
luteinising-hormone releasing hormone (LHRH). Bioavailability is almost
complete. Goserelin is poorly protein bound and has a serum elimination
half-life of two to four hours in patients with normal renal function. The
half-life increases with patients with impaired renal function. There is no
significant change in pharmacokinetics in subjects with hepatic failure. After
administration, peak serum concentrations are reached in about two hours. It
rapidly binds to the LHRH receptor cells in the pituitary gland thus leading to
an initial increase in production of luteinizing hormone and thus leading to an
initial increase in the production of corresponding sex hormones. This initial
flare may be treated by co-prescribing/co-administering Casodex (Bicalutamide)
or similar medication. Eventually, after a period of about 14–21 days,
production of LH is greatly reduced due to receptor downregulation, and sex
hormones are generally reduced to castrate levels.
Indications
Goserelin Acetate is used to treat hormone-sensitive cancers of the
breast (in pre- and peri- menopausal women) and prostate, and some benign
gynaecological disorders (endometriosis, uterine fibroids and endometrial
thinning). In addition, goserelin is used in assisted reproduction and in the
treatment of precocious puberty. It may also be used in the treatment of
male-to-female transsexuals and is favoured above other anti-androgens in some
countries, such as the UK. It is available as a 1-month depot and a long-acting
3-month depot.
Side effects
Goserelin Acetate may cause a temporary increase in bone pain and
symptoms of prostatic cancer during the first few weeks of treatment. This is
known as the tumour flare effect, and is the result of an initial increase in
luteinizing hormone production, before the receptors are desensitised and
hormonal production is inhibited. The symptoms will disappear, with hormonal
inhibition. It is therefore advisable to co-treat with an antiandrogen during
the first 2–3 weeks of Gosrelin treatment, particularly in patients with
pre-existing bone symptoms. Goserelin may cause bone pain, hot flushes,
headache, stomach upset, depression, difficulty urinating (isolated cases),
weight gain, swelling and tenderness of breasts (infrequent), decreased
erections and reduced sexual desire. Bone pain can be managed symptomatically,
and erectile dysfunction can be treated by Levitra (Vardenafil) or other
similar oral therapies.
