What is Zoladex (goserelin)?

What is Zoladex (Goserelin)?

Zoladex (goserelin acetate) is a synthetic gonadotropin-releasing hormone (GnRH) agonist administered as a subcutaneous biodegradable depot implant that suppresses sex hormone production by inhibiting pituitary gonadotropin secretion, primarily used for treating hormone-sensitive prostate cancer, breast cancer, and endometriosis. 1

Mechanism of Action

Goserelin works through a biphasic mechanism that initially stimulates, then suppresses hormone production 1:

• Initial phase: Causes a temporary increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a transient rise in testosterone (males) or estradiol (females) 1, 2
• Sustained phase: Chronic administration leads to sustained suppression of pituitary gonadotropins, reducing testosterone to castrate levels in men (within 2-4 weeks) and estradiol to postmenopausal levels in women (within 2-3 weeks) 1, 3
• This suppression is maintained throughout the duration of therapy 1, 4

Formulation and Administration

Zoladex is supplied as a sterile, biodegradable implant containing 3.6 mg of goserelin (equivalent to 3.8 mg goserelin acetate) designed for subcutaneous injection with continuous release over 28 days 1:

• The drug is dispersed in a biodegradable matrix of D,L-lactic and glycolic acids copolymer 1
• Administered monthly via a preloaded syringe with a 16-gauge needle 1
• A 3-month depot formulation (10.8 mg) is also available 4
• The biodegradable polymer is completely absorbed and has no antigenic potential 1

Clinical Applications

Prostate Cancer

Goserelin produces disease remission or stabilization in approximately 75% of men with previously untreated prostate cancer, with efficacy equivalent to surgical castration or diethylstilbestrol 2, 5:

• Used in combination with radiation therapy, goserelin significantly improves disease-free survival and overall survival in locally advanced disease 5
• In the landmark Bolla trial, radiation plus goserelin (3.6 mg every 4 weeks for 3 years) improved 5-year disease-free survival from 40% to 74% and overall survival from 62% to 78% 5
• Commonly combined with antiandrogens (flutamide, bicalutamide) for combined androgen blockade 5
• Standard dosing is 3.6 mg subcutaneously every 4 weeks 5

Breast Cancer

In premenopausal women with hormone receptor-positive breast cancer, goserelin achieves objective response rates of 30-45%, comparable to surgical oophorectomy 2, 3, 6:

• Adjuvant goserelin monotherapy has similar efficacy to adjuvant chemotherapy in premenopausal women with early, hormone receptor-positive breast cancer 7
• The ABCSG-12 trial demonstrated that adding goserelin (3.6 mg every 6 months for 3 years) to endocrine therapy reduced disease-free survival events by 29% 5
• Often combined with tamoxifen or aromatase inhibitors for complete endocrine blockade 5
• Provides a reversible alternative to surgical oophorectomy, allowing potential return of ovarian function after treatment 7

Endometriosis and Uterine Fibroids

Goserelin is effective for benign gynecological conditions 2:

• Six months of therapy relieves signs and symptoms of endometriosis 2
• Preoperative goserelin aids surgical removal of uterine leiomyomas and reduces blood loss 2

Pharmacokinetics

When administered as a solution, goserelin is rapidly absorbed and eliminated with a mean half-life of 4.2 hours in males and 2.3 hours in females 4:

• The depot formulation's release profile is determined by the biodegradable polymer matrix over 1 or 3 months 4
• No clinically relevant accumulation occurs with multiple depot administrations 4
• Extensively metabolized prior to excretion 4
• No dose adjustment needed in elderly patients or those with hepatic or renal impairment 1, 4

Common Side Effects

The most frequent adverse effects relate to sex hormone suppression 1, 2:

• Hot flushes: Occur in the majority of patients due to estrogen/testosterone suppression 1, 2
• Loss of libido: Common in both men and women 2
• Tumor flare: Initial testosterone elevation can cause disease flare in prostate cancer patients (bone pain, urinary obstruction) 2
• Bone loss: Prolonged use can lead to decreased bone mineral density 5
• Generally well tolerated with low withdrawal rates (4-10%) 5

Important Clinical Considerations

A critical pitfall is the initial tumor flare phenomenon in prostate cancer patients, which can be prevented by concurrent antiandrogen therapy (e.g., cyproterone acetate, flutamide) started before or with goserelin 5, 8:

• The initial rise in testosterone can worsen symptoms in the first 2-4 weeks 1, 2
• Antiandrogens should be given for at least the first month of therapy 5

For bone health protection, patients on long-term goserelin therapy should receive calcium and vitamin D supplementation, with bisphosphonates considered for those at high fracture risk 5:

• Particularly important in breast cancer patients receiving aromatase inhibitors plus goserelin 5
• Zoledronic acid (4 mg every 6 months) effectively prevents bone loss in this setting 5