Goserelin
| Evidence Level: L1 | Predicted Indications: 3 |
Table of Contents
- Goserelin
- Goserelin: From a GnRH Agonist Implant to Ovarian Function Preservation During Chemotherapy (Predicted: Amenorrhea)
Goserelin: From a GnRH Agonist Implant to Ovarian Function Preservation During Chemotherapy (Predicted: Amenorrhea)
One-Sentence Summary
Goserelin is a GnRH agonist marketed in the US as the ZOLADEX implant; its approved indication is not recorded in the license data. The TxGNN model predicts it may be effective for amenorrhea. The supporting trials actually test protecting ovarian function during chemotherapy, so the claim should be worded that way rather than as treating amenorrhea. This direction is supported by 7 clinical trials (3 completed Phase 3 RCTs) and 20 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the US license records |
| Predicted New Indication | Amenorrhea (best read as ovarian function preservation during chemotherapy) |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L1 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 2 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Goserelin is a GnRH agonist. After an initial flare, it desensitizes the pituitary and suppresses LH/FSH and ovarian estradiol. This causes reversible amenorrhea.
The “amenorrhea” label in the knowledge graph describes a pharmacological effect and an outcome target, not a condition to be treated. The Phase 3 trials use this effect on purpose. Temporary ovarian suppression during chemotherapy is thought to protect the follicle pool and reduce chemotherapy-induced premature ovarian failure and amenorrhea. The original-versus-new indication link is therefore about protecting fertility and ovarian function in premenopausal breast cancer patients on gonadotoxic chemotherapy. It does not support use for amenorrhea from other causes.
The mechanistic explanation comes from the pack’s repurposing rationale, since no separate MOA entry is available.
The other two predictions, renal hypoplasia and bilateral renal hypoplasia (scores about 0.99), have no trials, no literature and no plausible mechanism. They are likely knowledge-graph artifacts (see the Conclusion).
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00427245 | Phase 3 | Completed | 400 | OPTION trial. Goserelin vs no goserelin to prevent early menopause in premenopausal stage I–III breast cancer patients on chemotherapy |
| NCT00068601 | Phase 3 | Completed | 257 | LHRH analog (goserelin) during chemotherapy to reduce ovarian failure in early-stage, hormone-receptor-negative breast cancer |
| NCT02483767 | Phase 3 | Completed | 98 | Randomized trial of chemotherapy with or without goserelin for ovarian function preservation in premenopausal breast cancer |
| NCT03475758 | Phase 2 | Unknown | 100 | Goserelin for ovarian protection during cyclophosphamide-containing chemotherapy; menstruation outcome |
| NCT02132390 | Phase 3 | Unknown | 300 | Adjuvant toremifene with or without goserelin in premenopausal breast cancer. Primary aim is oncologic, so only indirectly relevant |
| NCT01218581 | Phase 2/3 | Completed | 32 | Aromatase inhibitors vs GnRH agonists for uterine adenomyosis. Different disease, so only indirectly relevant |
| NCT00488722 | N/A | Unknown | Not reported | Single-arm study of Zoladex 3.6 mg plus CEF chemotherapy as neoadjuvant therapy in premenopausal breast cancer. Weak relevance |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28472240 | 2017 | Meta-analysis | Ann Oncol | OPTION trial. Tested whether a GnRH agonist during chemotherapy for early breast cancer reduces the risk of premature ovarian insufficiency |
| 12488406 | 2002 | RCT | J Clin Oncol | Goserelin vs CMF as adjuvant therapy in premenopausal node-positive breast cancer (ZEBRA); addresses premature menopause effects |
| 14679153 | 2003 | RCT | J Natl Cancer Inst | IBCSG Trial VIII. Chemotherapy followed by goserelin vs either alone in node-negative premenopausal breast cancer |
| 17159194 | 2007 | RCT secondary analysis | J Clin Oncol | Impact of chemotherapy, goserelin or both on amenorrhea, hot flashes and quality of life |
| 21325445 | 2011 | Long-term RCT follow-up | Ann Oncol | Long-term results of IBCSG Trial VIII comparing goserelin, CMF and CMF followed by goserelin |
| 12353820 | 2002 | Review | Breast Cancer Res Treat | Overview of LHRH agonists in early breast cancer; goserelin induces reversible ovarian ablation |
| 12734855 | 2003 | Review | Br J Surg | Review of methods of ovarian ablation in adjuvant treatment of premenopausal breast cancer |
| 1533675 | 1992 | Review | J R Army Med Corps | Goserelin as a way to induce amenorrhoea, discussed for female personnel mobilised for war |
| 25187267 | 2015 | Cohort | Cancer Res Treat | Goserelin ovarian ablation in stage II/III hormone-receptor-positive breast cancer without chemotherapy-induced amenorrhea |
| 2522795 | 1989 | Small clinical study | Br J Obstet Gynaecol | In 12 women with premature ovarian failure, goserelin-induced gonadotrophin suppression did not reverse the failure |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA019726 | ZOLADEX (TerSera Therapeutics LLC) | Implant | Not listed in the record |
| NDA020578 | ZOLADEX (TerSera Therapeutics LLC) | Implant | Not listed in the record |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Three completed Phase 3 RCTs and several large RCT publications support goserelin for ovarian function preservation during chemotherapy, giving L1 evidence. The “amenorrhea” label is a pharmacological effect, so the claim must be worded as “ovarian function preservation during chemotherapy”, not “treatment of amenorrhea”. The renal hypoplasia predictions (ranks 2 and 3) have no evidence and no plausible mechanism, and remain on Hold at L5.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are not yet obtained and block the safety screening
- Formal MOA data from DrugBank
- Confirmation that NCT02483767 uses goserelin, since the trial title names only “GnRH agonist”
- The approved indication text for the two NDAs
- Guardrails: limit use to premenopausal breast cancer patients on gonadotoxic chemotherapy, with counseling on fertility and hormone-receptor status; no use for primary or secondary amenorrhea from other causes
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.