Goserelin (Zoladex) - GnRH Agonist for Hormone-Dependent Cancers — Reproduction
FDA-approved GnRH agonist implant for prostate cancer, breast cancer, and endometriosis via sustained testosterone/estrogen suppression.
Overview
Goserelin acetate (Zoladex) is an FDA-approved GnRH agonist (1989) for hormone-dependent cancers and conditions. REGULATORY: FDA-approved for advanced prostate cancer (palliative), locally confined prostate cancer (with flutamide + radiation), advanced breast cancer in pre/perimenopausal women (ONLY GnRH agonist with this indication), endometriosis, and endometrial thinning. Available as 3.6 mg (monthly) or 10.8 mg (quarterly) SC implant in 125+ countries. CLINICAL EVIDENCE: RTOG 85-31 (n=945): 84% vs 71% local recurrence-free at 5 years (P<0.0001). NEJM 1997 (n=415): Improved local control and survival with radiation. SWOG-8692: Equivalent to oophorectomy in metastatic breast cancer. POEMS (n=257, NEJM 2015): Ovarian failure 8% vs 22% with goserelin during chemo (P=0.04). IBCSG VIII (n=1,063): Goserelin equals CMF chemo for ER+ disease. Meta-analysis: 10 of 11 major Phase III trials with ADT+RT used goserelin. MECHANISM: GnRH receptor downregulation → LH/FSH suppression → medical castration. 95% achieve testosterone ≤50 ng/dL by week 4.
Indications
- Advanced prostate cancer (palliative androgen deprivation)
- Breast cancer (pre/perimenopausal ER+ advanced disease)
- Endometriosis (symptom management)
- Endometrial thinning (pre-ablation or pre-resection)
- Gender-affirming hormone therapy (off-label)
Mechanism of Action
Prostate cancer: testosterone-dependent. Breast cancer: estrogen-dependent. Endometriosis: estrogen-driven
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Goserelin acetate 3.6 mg SC implant | 3.6 mg SC | Every 28 days | Implant in abdominal wall; add bicalutamide 50 mg daily for first 4 weeks to prevent testosterone flare |
| Goserelin acetate 10.8 mg SC implant | 10.8 mg SC | Every 12 weeks (quarterly) | Implant in abdominal wall; reduces injection frequency; add antiandrogen for first dose |
| Goserelin acetate 3.6 mg SC implant | 3.6 mg SC | Every 28 days | Pre/perimenopausal ER+ advanced breast cancer; often combined with tamoxifen or aromatase inhibitor |
| Goserelin acetate 3.6 mg SC implant | 3.6 mg SC | Every 28 days for maximum 6 months | Add-back therapy (estrogen/progesterone) recommended after 3 months |
Evidence Grade
GRADE A
Safety & Contraindications
- ⚠️ PRESCRIPTION MEDICATION - Oncology/endocrinology supervision required
- TESTOSTERONE FLARE: First 2-3 weeks may worsen prostate cancer symptoms (bone pain, spinal cord compression, urinary obstruction) - add antiandrogen (bicalutamide) for first 4 weeks
- Cardiovascular risks: ↑MI, stroke, sudden cardiac death with long-term ADT
- Metabolic syndrome: Weight gain, insulin resistance, dyslipidemia, diabetes
- Bone loss: Significant osteoporosis risk - DEXA screening, calcium/vitamin D, consider bisphosphonates
- Hot flashes (70-80%): Most common; may use low-dose estrogen or venlafaxine
- Sexual dysfunction: Erectile dysfunction, loss of libido (expected)
- Tumor flare in breast cancer: May cause transient disease flare in first weeks
- Implant site reactions: Local pain, bruising at SC injection site
- NOT for pregnancy (Category X/D depending on indication)