Goserelin
| 證據等級: L5 | 預測適應症: 3 個 |
目錄
Goserelin: From Hormone-Responsive Breast Cancer to Amenorrhea
One-Sentence Summary
Goserelin is a GnRH (LHRH) agonist whose established clinical use — per the trial evidence in this pack — is in hormone-responsive breast cancer (ovarian suppression/protection during chemotherapy) and endometriosis-related pelvic pain. The TxGNN model predicts it may be effective for Amenorrhea, which is mechanistically consistent with its known pharmacology (pituitary desensitization → suppressed FSH/LH → induced reversible amenorrhea), and is supported by 7 clinical trials (3 completed Phase 3 RCTs) and 19 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not formally recorded in this evidence pack (no Taiwan license data); trial context indicates hormone-responsive breast cancer / endometriosis |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L1 |
| Market Status (Taiwan) | Not Marketed |
| Number of Licenses | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed formal mechanism-of-action data for Goserelin is not available in this evidence pack (original_moa: [Data Gap]). Based on the mechanistic rationale attached to this prediction, however, Goserelin is a GnRH agonist: continuous administration causes pituitary desensitization, suppressing FSH/LH secretion, which in turn suppresses ovarian steroidogenesis and ovulation and directly induces reversible amenorrhea. This is an established pharmacological mechanism, not a speculative link — it is the same mechanism already exploited clinically to protect ovarian function during chemotherapy and to induce therapeutic amenorrhea in endometriosis/fibroid management.
Importantly, “amenorrhea” in this context is largely a therapeutic/protective goal (preventing chemotherapy-induced ovarian failure) rather than amenorrhea being treated as a disease endpoint in itself. This distinction matters for how the indication should be framed clinically and regulatorily — it is closer to a label-consistent extension of known use than a mechanistically novel repurposing.
Given the drug’s demonstrated ability to induce ovarian suppression is already well documented across multiple large Phase 3 oncology trials, the TxGNN prediction is well grounded rather than a purely algorithmic artifact.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02483767 | Phase 3 | Completed | 98 | RCT evaluating goserelin for ovarian function preservation during chemotherapy in premenopausal breast cancer |
| NCT00068601 | Phase 3 | Completed | 257 | LHRH analog during chemotherapy to reduce ovarian failure in early-stage, hormone-receptor-negative breast cancer |
| NCT00427245 | Phase 3 | Completed | 400 | OPTION trial — goserelin for prevention of early menopause during chemotherapy in stage I–III premenopausal breast cancer |
| NCT03475758 | Phase 2 | Unknown | 100 | Goserelin for ovarian protection with cyclophosphamide-containing chemotherapy; menstruation outcome endpoint |
| NCT01218581 | Phase 2/3 | Completed | 32 | Aromatase inhibitors vs. GnRH agonists for uterine adenomyosis management |
| NCT02132390 | Phase 3 | Unknown | 300 | Adjuvant toremifene ± goserelin in HR-positive breast cancer with/without chemotherapy-induced amenorrhea |
| NCT00488722 | NA | Unknown | N/A | Single-arm study of Zoladex 3.6mg + CEF as neoadjuvant therapy in hormone-responsive premenopausal breast cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17159194 | 2007 | RCT | J Clin Oncol | IBCSG Trial VIII — QOL and amenorrhea/hot flashes with chemo vs. goserelin vs. sequential combination |
| 12488406 | 2002 | RCT | J Clin Oncol | ZEBRA study — goserelin vs. CMF chemotherapy as adjuvant therapy in node-positive premenopausal breast cancer |
| 28472240 | 2017 | RCT | Ann Oncol | OPTION trial — GnRH agonist during chemotherapy protects against ovarian toxicity/premature ovarian insufficiency |
| 14679153 | 2003 | RCT | J Natl Cancer Inst | Adjuvant chemotherapy followed by goserelin vs. either modality alone in node-negative premenopausal breast cancer |
| 8513962 | 1993 | RCT | Fertil Steril | Goserelin vs. low-dose oral contraceptive for endometriosis-associated pelvic pain |
| 25187267 | 2015 | Cohort | Cancer Res Treat | Ovarian ablation with goserelin improves survival in stage II/III HR-positive breast cancer without chemo-induced amenorrhea |
| 26951320 | 2016 | Cohort/Observational | J Clin Oncol | Discussion of estradiol monitoring necessity during ovarian suppression for breast cancer |
| 1533675 | 1992 | Review | J R Army Med Corps | Review of methods to induce amenorrhea, including the GnRH analogue goserelin |
| 12734855 | 2003 | Review | Br J Surg | Review of ovarian ablation methods in adjuvant treatment of premenopausal/perimenopausal breast cancer |
| 12353820 | 2002 | Review | Breast Cancer Res Treat | Overview of LHRH agonists in early breast cancer — benefits of reversible ovarian ablation |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Evidence Level L1 is met — three completed Phase 3 RCTs (NCT02483767, NCT00068601, NCT00427245) plus corroborating RCT-level literature (IBCSG Trial VIII, ZEBRA, OPTION) directly support goserelin-induced ovarian suppression/amenorrhea in a well-characterized clinical population. However, the drug is currently not marketed in Taiwan (0 licenses), and drug-level safety documentation (warnings, contraindications, DDI) is entirely a data gap.
To proceed, the following is needed:
- TFDA package insert (warnings/contraindications) — flagged as a Blocking gap (DG001); required before any S1 safety screening
- Formal DrugBank/MOA documentation to replace the inferred mechanistic rationale (DG002)
- Confirmation of original approved indication(s), since no Taiwan license records exist for this drug
- Clarification of intended clinical positioning — protective/therapeutic amenorrhea induction (e.g., during chemotherapy) vs. amenorrhea as a standalone treatment target
- DDI data (currently
not_found) before combination-therapy use cases are considered
Note: Two additional TxGNN-predicted candidates for this drug (renal hypoplasia, renal hypoplasia bilateral) were also screened but scored Evidence Level L5 with no supporting trials or literature and no plausible mechanistic link — both are recommended Hold and are not carried forward in this report.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.