Mifepristone in Oncology
Repurposing rationale, mechanisms, evidence by cancer type, combinations, dosing and timing patterns, safety and international access
Mifepristone, also called RU-486. Evidence includes laboratory studies, animal research, early human trials, randomised trials and case reports. These categories are kept separate. This is a targeted narrative review, not an exhaustive systematic review or a live trial-recruitment directory. References with full titles and source links are found at the end.
Quick jump menu
5. Anticancer combinations and possible synergies
6. Dosing, scheduling and treatment timing
7. Safety and side-effect management
8. Safety and interaction issues
9. International sourcing and access
10. Connected work notes and evidence gaps
1. Overview
Mifepristone is an established prescription medicine that blocks progesterone receptors and glucocorticoid receptors. Depending on product and country, its licensed uses include pregnancy termination and treatment of high blood sugar caused by excess cortisol in selected adults with endogenous Cushing's syndrome. Cancer-directed use is investigational/off-label rather than an established general oncology indication.
The oncology rationale has two main branches. One targets progesterone-related growth signals in selected tumours. The other targets glucocorticoid-related survival signals that may help cancer cells resist another treatment. Neither approach means that every progesterone-receptor-positive tumour will respond, or that progesterone-receptor-negative cancer cannot be relevant to research.
Human evidence is mixed. A short biomarker-selected breast-cancer study found reduced cell-proliferation markers. A small randomised triple-negative breast-cancer trial did not improve progression-free survival with the tested chemotherapy combination. A larger placebo-controlled meningioma trial found no benefit. Case reports describe potentially important responses in other cancers but cannot establish how reliably patients benefit.
2. Drug-repurposing rationale
Why researchers are interested
Cancer cells receive chemical messages through receptors. Some messages influence cell division; others help cells survive stress or treatment. Researchers are investigating whether blocking particular hormone-related messages makes selected cancers less able to grow or recover after treatment.
Proposed roles include:
Blocking progesterone-driven growth in a biologically selected tumour.
Reducing glucocorticoid-receptor signalling that may protect some cancer cells from chemotherapy.
Limiting regrowth between treatment exposures.
Altering immune-related signals or the tumour environment.
Modifying drug transport, DNA-damage repair or treatment sensitivity in selected laboratory models.
An oral medicine with existing pharmacology and manufacturing is a practical repurposing candidate. However, evidence from a single reproductive-health dose does not establish the safety of daily treatment over months, and Cushing's-syndrome dosing is not automatically an oncology regimen.
Three treatment intentions to keep separate
Intended role | What researchers aim to achieve | What would support the claim? |
Direct growth suppression | Slow tumour-cell division or promote cell death. | Tumour/biomarker changes, then controlled clinical outcomes. |
Treatment sensitisation | Make another treatment more effective by reducing a survival or resistance signal. | A comparison against the same partner treatment without mifepristone. |
Immune/environmental modulation | Change conditions that may protect the tumour from immune attack. | Verified biological changes and improved patient outcomes; not immune-marker changes alone. |
Receptor positivity is a starting point, not a complete selection tool
Routine pathology usually reports overall progesterone-receptor positivity, not the ratio of its two principal forms, PRA and PRB. The MIPRA study used a specialised PRA/PRB assessment. Routine PR positivity alone does not reproduce its selection process.
Similarly, glucocorticoid-receptor staining does not necessarily show how strongly its pathway is operating. In the small randomised TNBC trial, GR expression did not significantly predict response to the combination.
3. Mechanism of action
A plain-language explanation
Hormones carry messages to cells. Receptors are the receiving points for those messages. Mifepristone can occupy certain receptors and interfere with the instructions they pass on.
It blocks progesterone messages. In some tumours, these messages help cells grow. It also blocks messages from cortisol and related steroid medicines. In selected cancer models, these signals help cells survive treatment, so blocking them may make treatment damage harder to withstand.
The same receptors also have important jobs in healthy tissues. Blocking them can affect pregnancy, the uterine lining, the body's response to illness and medicines such as dexamethasone. The treatment rationale and safety issues therefore arise from some of the same actions.
Mechanism | What happens | Relevance to cancer treatment |
Progesterone-receptor modulation/antagonism | Alters progesterone-related gene signals; effects depend partly on receptor form and cell context. | Rationale for selected PR-driven tumours; not a universal response across PR-positive cancers. |
Glucocorticoid-receptor blockade | Interferes with cortisol-related gene signals. | May reduce selected cancer-cell survival responses to chemotherapy; also interferes with medically needed steroids. |
Cell-cycle effects | Some experiments show reduced CDK2 activity and arrest before DNA replication. | May suppress growth even in selected cells lacking classical nuclear PR. Human benefit is not established by cell arrest alone. |
DNA repair and drug transport | Glioma models show changes in MGMT, P-glycoprotein and temozolomide exposure. | Possible sensitisation; not proof that mifepristone reverses clinical temozolomide resistance. |
Immune-related changes | Changes in lymphocyte infiltration and immune-associated pathways were seen in selected breast tumours; PIBF suppression is a separate proposed mechanism. | These observations and hypotheses need separate evaluation, not a general claim of immune restoration. |
Hormonal feedback | Receptor blockade can increase circulating cortisol and other downstream hormones. | Blood cortisol may rise despite blocked action; in prostate cancer, increased androgens may work against the treatment intention. |
PRA and PRB: two forms of the progesterone receptor
PRA and PRB are two versions of the receptor, produced from the same gene. The balance between them can affect how a tumour responds. Preclinical work behind MIPRA found inhibition in PRA-dominant models, while some PRB-dominant models showed no benefit or stimulation of growth/metastatic behaviour. This is a laboratory concern, not proof that mifepristone worsens every PRB-dominant human cancer. It nevertheless argues against assuming that blocking progesterone is automatically beneficial.
4. Evidence by cancer type
Cancer/tumour type | Evidence identified | Interpretation |
Luminal, ER+/PR+ breast cancer | MIPRA: 20 selected postmenopausal patients, PRA/PRB >1.5 and PR ≥50%, received 200 mg/day for 14 days before surgery. Fourteen met the prespecified Ki67 reduction criterion. | Human proof of biological activity in a selected group; not a survival or recurrence-prevention trial. |
Triple-negative breast cancer | A 2025 randomised phase II trial enrolled 29 of a planned 64 patients; nab-paclitaxel with or without intermittent mifepristone. Median progression-free survival was 3 months in both arms. | No demonstrated added PFS or response-rate benefit in this underpowered trial; combination increased severe neutropenia. |
Advanced breast and epithelial ovarian cancer | A 2025 publication of a phase I carboplatin/gemcitabine/mifepristone trial enrolled 31 patients. Among 25 evaluable patients, two complete and two partial responses were reported. | Early combination activity, but no control group to isolate mifepristone. Neutropenia required chemotherapy reductions and growth-factor support. |
Ovarian, fallopian-tube and primary peritoneal cancer | Historical single-agent phase II studies used 200 mg/day. Laboratory studies also investigated suppressing regrowth between cisplatin exposures. | This draft identifies the older studies but does not provide an extracted response-rate comparison; it does not establish single-agent effectiveness. |
Meningioma | SWOG S9005: 164 eligible patients; 200 mg/day versus placebo for up to 2 years, with continuation possible. No significant failure-free or overall-survival benefit. | The strongest negative randomised evidence in this report. PR expression alone did not translate into benefit. Meningioma is distinct from glioblastoma and is often non-malignant. |
Glioma / glioblastoma | Cell and animal studies of temozolomide ± radiation show sensitisation and changes in resistance pathways. Isolated clinical reports describe palliation. | Human survival benefit with the combination has not been established by the evidence reviewed here. Steroid dependence is a major practical issue. |
Castration-resistant prostate cancer | A 19-patient phase II trial used 200 mg/day. No >50% PSA responses; six patients had stable disease for a median 5.5 months. Androgens increased. | Limited activity; hormonal feedback can undermine the intended effect. Do not present receptor antagonism as uniformly beneficial. |
Non-small-cell and small-cell lung cancer | Case reports and a 2025 six-patient report: four NSCLC, two SCLC, treated with 200 or 300 mg/day. Authors reported 66.7% 5-year overall survival. | Four survivors out of six selected cases, not an expected response/survival rate for future patients. No randomised comparator; attribution and generalisability remain uncertain. |
Cervical cancer | Laboratory and animal work with cisplatin/chemoradiation. | Preclinical sensitisation; no validated human regimen established here. |
Endometrial cancer | Laboratory growth studies include PR-negative contexts. | Not a treatment recommendation: the chronic-use KORLYM label contraindicates use in endometrial carcinoma or atypical hyperplasia. Research and product contraindications must not be conflated. |
Renal and pancreatic cancer | Individual reports, summarised in the glioma review, describe palliative benefit/long survival. | Case-level signals; no reliable efficacy estimate or proof of causation. |
Other solid tumours / leukaemia | Laboratory studies and scattered case reports are described in the broader literature. | This version does not claim completed original-paper evaluation for every cancer. |
Interpreting the lung-cancer report
The six-patient paper deserves inclusion rather than dismissal, but its title is not a population-level estimate. Mixed lung-cancer types, previous treatment, patient selection, the timing from which survival is counted and assessment of quality of life all affect interpretation. The abstract's conclusion that chance is very unlikely is the authors' interpretation, not a substitute for a comparator or a prespecified statistical study design.
5. Anticancer combinations and possible synergies
A biological rationale, additive cell killing, formal laboratory synergy and improved clinical outcomes are different findings. The table records what was tested without treating them as equivalent.
Combination | Evidence/rationale | Clinical interpretation |
Nab-paclitaxel | GR blockade may reduce chemotherapy-survival signals; phase I activity preceded the randomised TNBC study. | The randomised study did not improve PFS/response rate. More neutropenia and altered paclitaxel clearance matter. |
Carboplatin + gemcitabine | Phase I human trial intended to test GR blockade with chemotherapy not appreciably dependent on CYP metabolism. | Responses occurred but marrow toxicity remained substantial. Avoid assuming that removing one pharmacokinetic interaction removes all toxicity. |
Temozolomide ± radiation | Glioblastoma cell/animal studies suggest sensitisation through several resistance pathways. | No established clinical survival benefit or universal timing schedule. |
Cisplatin | Cervical cell/animal studies found increased cytotoxicity; ovarian-cell experiments tested post-cisplatin regrowth suppression. | Model-specific preclinical findings; not a universal platinum protocol. |
Tamoxifen / other endocrine partners | MIPRA authors discuss preclinical rationale for tamoxifen combinations in PRA-dominant disease. | Clinical evaluation is needed. Do not assume equivalence with aromatase inhibitors or ER degraders; PR expression can change. |
Pembrolizumab | Phase II HER2-negative breast-cancer study tested daily mifepristone with pembrolizumab. | Not an established pairing. Registry notes serious rash concerns after recent radiation; steroid rescue is a major consideration. |
Enzalutamide / AR-directed approaches | GR signalling is a resistance hypothesis in prostate and selected breast settings. | This draft does not establish benefit or a current trial-access pathway. Feedback and metabolism interactions require review. |
2-DG, metformin or diclofenac | These drugs address different proposed pathways, but a multi-pathway rationale does not establish a specific mifepristone combination. | No verified oncology efficacy study for these particular pairings is included in this draft. Safety issues can still be identified, including QT and CYP2C9-related risks. |
5A. Selected hormone-receptor-positive breast cancer: the MIPRA study
What was studied?
MIPRA was a single-arm presurgical window study: a short treatment period between diagnosis and planned surgery. Twenty postmenopausal patients with untreated luminal cancers were selected for PR expression of at least 50% and PRA/PRB >1.5, determined by Western blot. They received oral mifepristone 200 mg daily for 14 days; surgery was on day 15.
Findings
The study reported a median relative reduction in Ki67 of approximately 49.6%. Ki67 is a marker of cell proliferation. Fourteen of 20 patients met the prespecified response criterion of at least a 30% relative reduction. Tissue studies also found changes in immune-related processes and cell-growth pathways.
This is not a 70% tumour-shrinkage rate, a 70% cure rate or a 49.6% reduction in total tumour burden. The principal result concerns Ki67 over two weeks. Without a placebo group, longer follow-up and recurrence/survival outcomes, the study cannot establish long-term benefit.
Selection and access to testing
Routine PR staining measures combined receptor expression and does not normally provide the specialised PRA/PRB ratio used here. The authors reported difficulties obtaining adequate material for Western blot and called for better companion diagnostics. A clinic should explain whether it can reproduce the relevant testing rather than treating a standard PR-positive result as equivalent.
Combination implications
The authors propose evaluating combinations with tamoxifen. They also raise the possibility that treatments reducing PR expression, such as some estrogen-depleting/degrading strategies, could affect the rationale. These are mechanistic considerations and research hypotheses—not instructions to stop an effective endocrine medicine. Each combination needs evidence and pharmacology review.
5B. Triple-negative breast cancer: mifepristone with nab-paclitaxel
Rationale
Some TNBC cells use GR signalling to resist chemotherapy-induced cell death. Because TNBC lacks routine PR positivity, the rationale here is mainly GR blockade, not blocking classical PR-positive growth.
The randomised 2025 publication
The trial stopped early because of poor accrual: 29 of 64 planned patients enrolled. It compared nab-paclitaxel with placebo against nab-paclitaxel with mifepristone 300 mg the day before and day of each chemotherapy dose.
Median PFS was 3.0 months in both groups. Reported response rates were 23% with the combination versus 31.5% with chemotherapy alone. An overall-survival trend was not statistically significant and was strongly influenced by one long-term responder. These data do not demonstrate added benefit, although the small sample limits precision.
Severe neutropenia occurred in 46% versus 7%, and febrile neutropenia in 23% versus 7%, with combination versus control. More patients needed chemotherapy dose reductions. These study-specific figures are not universal mifepristone risk estimates.
More than one explanation for a stronger drug effect
Mifepristone inhibits CYP2C8/CYP3A4, enzymes involved in paclitaxel metabolism. It may increase chemotherapy exposure as well as alter tumour signalling. A stronger anticancer or toxic effect cannot automatically be attributed to receptor-level synergy. Nab-paclitaxel was also relevant because it reduces the routine need for steroid premedication; other taxane formulations are not automatically interchangeable in this strategy.
5C. Carboplatin + gemcitabine + mifepristone
The phase I study published in 2025 enrolled 31 patients with advanced breast or recurrent/persistent epithelial ovarian cancer. Twenty-five were evaluable for response: two complete responses, two partial responses, 13 stable disease and eight progression. One ovarian-cancer patient had a prolonged complete response lasting over 63 months at the reported follow-up.
These findings warrant study, but carboplatin and gemcitabine are active drugs. Without a comparator, the added contribution of mifepristone is unknown. Responses occurred at higher gemcitabine dose levels; none were observed at lower levels, which also illustrates the difficulty of balancing activity against toxicity.
The reported recommended phase II combination was carboplatin AUC 2 plus gemcitabine 600 mg/m² on days 1 and 8 of a 21-day cycle, mifepristone 300 mg on the day before and day of each chemotherapy administration, and pegylated G-CSF on day 9. This is a historical research regimen, not an individual recommendation.
Higher-than-expected neutropenia led to chemotherapy reductions and growth-factor support. A regimen designed to avoid CYP-mediated chemotherapy interactions can still have pharmacodynamic effects on healthy tissues. The publication also contains inconsistencies in dose-level/DLT wording; this draft uses its stated final regimen rather than attempting to resolve a prescribing protocol from the article alone.
5D. Glioblastoma: temozolomide and radiation research
A 2021 review brings together cell and animal studies suggesting that mifepristone can improve temozolomide or chemoradiation effects. Proposed mechanisms include reduced MGMT protein, altered P-glycoprotein, changed brain/tumour drug exposure and reduced VEGF.
MGMT helps repair one type of temozolomide-related DNA damage. Lowering its protein in an experimental model is not equivalent to proving a change in a patient's MGMT promoter methylation status or overcoming clinical resistance.
A major practical tension is dexamethasone. It may be needed to control brain swelling, while mifepristone blocks its receptor-mediated effects. Do not stop dexamethasone abruptly or omit needed brain-oedema treatment in pursuit of a laboratory rationale. Any proposal requires an agreed neuro-oncology and steroid/emergency plan.
5E. Immune modulation, PIBF and checkpoint combinations
What has been observed?
MIPRA found changes in immune-related pathways and increased tumour-infiltrating lymphocytes in selected tissue samples. This does not establish that an immune-checkpoint combination improves survival.
The PIBF hypothesis
Progesterone-induced blocking factor (PIBF) is an immune-modulating protein. Some investigators propose that reducing progesterone-related immune suppression, including PIBF, could help control cancers lacking classical nuclear PR. This hypothesis appears in the lung-cancer case literature and broader reports.
The hypothesis should not be presented as a proven explanation for every clinical response. Nuclear PR, membrane-related progesterone signalling, PIBF and GR are distinct concepts; the evidence for one cannot simply substitute for another.
Checkpoint treatment and steroid rescue
The pembrolizumab study NCT03225547 used daily mifepristone starting one week before pembrolizumab. The accessible NCI listing says closed to accrual. A 2026 secondary review reports termination due to side effects; this draft does not treat the secondary status summary as a complete final efficacy/safety report.
The registry excludes recent radiation because serious rashes had been observed and includes multiple steroid-related exclusions. Checkpoint adverse events can require systemic corticosteroids. A GR-blocking medicine can complicate rescue, so a protocol must anticipate that conflict. It is not sufficient to say the two drugs both support immune activity.
6. Dosing, scheduling and treatment timing
The following are published research patterns or labelled non-cancer use. They are not interchangeable and do not establish an anticancer dose for an individual.
Setting | Dose/schedule | Interpretation |
MIPRA breast-cancer window study | 200 mg orally daily for 14 days, then surgery on day 15. | Short biomarker-selected monotherapy study; not a maintenance prescription. |
TNBC randomised trial | 300 mg the day before and day of nab-paclitaxel, with chemotherapy on days 1, 8 and 15 of a 28-day cycle. | Intermittent sensitisation strategy; PFS did not improve. |
Carboplatin/gemcitabine trial | 300 mg the day before and day of each day-1/day-8 chemotherapy exposure in a 21-day cycle, with food. | Combination-specific phase I regimen requiring substantial marrow monitoring/support. |
Meningioma phase III | 200 mg daily for up to 2 years, with continuation possible. | No failure-free or survival benefit versus placebo. |
Prostate phase II | 200 mg daily until progression. | Limited activity with increased androgen levels. |
Lung-cancer six-patient report | 200 or 300 mg daily. | Case-series exposure, not a validated lung-cancer dose. |
Historical ovarian monotherapy studies | 200 mg daily; one study used 28-day cycles. | Research patterns, not an established effective schedule. |
KORLYM for selected Cushing's syndrome | Label starts at 300 mg once daily with a meal; titration and limits depend on response, organ function and interactions. | Non-oncology indication. Its higher licensed dose range must not be copied into cancer treatment. |
Food and formulation
The KORLYM label directs taking the medicine with a meal and swallowing tablets whole, without splitting, crushing or chewing. Food increases exposure. Follow the actual supplied product and study/prescriber instructions; different brands and strengths should not be substituted informally.
Accumulation and washout
After repeated 600 mg/day dosing, the label reports a mean terminal half-life of about 85 hours, with substantial variability. Steady state can take around two weeks. That measurement is context-specific, but demonstrates why effects do not end with the last tablet.
The label advises at least two weeks after stopping KORLYM before initiating or increasing interacting medicines. This is not a universal instruction to withhold urgently needed care: emergency clinicians must be told the exposure and manage accordingly. Separating medicines by a few hours does not resolve enzyme inhibition or receptor blockade.
Exposure limitations
MIPRA measured total plasma concentrations around 0.7 micromolar at its sampling times. Some laboratory anticancer experiments use higher micromolar exposure. Differences in sampling, active metabolites, protein binding and tumour exposure prevent simple conversion between cell-culture concentrations and tablet doses. More milligrams do not produce proportional exposure.
7. Safety and side-effect management
Important context
Chronic-use safety information is drawn substantially from Cushing's syndrome, where cortisol biology differs from that of many cancer patients. For example, hypokalaemia occurred in 44% of participants in the cited Cushing's study; that is not an oncology risk estimate. Conversely, mild short-term effects in a 14-day breast study do not establish safety over months.
Main areas to monitor
Area | Concern | Practical monitoring/discussion |
Glucocorticoid blockade / adrenal insufficiency | Weakness, marked fatigue, nausea, low blood pressure or low glucose can occur. Cortisol may remain high. | A clinical emergency/rescue plan; do not rely on a normal/high cortisol result to exclude functional glucocorticoid deficiency. |
Potassium | Low potassium can cause weakness and increase arrhythmia risk. | Correct before treatment; label recommends testing 1–2 weeks after starting/increasing and periodically thereafter. Individualise for oncology. |
QTc / heart rhythm | Dose-related QT prolongation; risk increases with low potassium and other QT drugs. | Review ECG, electrolytes, other medicines and symptoms. |
Uterine lining and bleeding | Endometrial thickening, cystic changes and unexpected bleeding. | Baseline bleeding/gynaecological history; investigate new bleeding rather than assuming it is harmless. |
Pregnancy | Potent antiprogestational effects can cause pregnancy loss. | Pregnancy exclusion and an appropriate non-hormonal contraception plan where applicable. |
Blood counts with chemotherapy | Neutropenia and febrile neutropenia increased in studied combinations. | Protocol-based counts, dose decisions and growth-factor support; fever instructions remain essential. |
Blood pressure/fluid balance | Hypertension and oedema can occur, particularly in hypercortisolism. | Monitor blood pressure, weight/fluid changes and relevant cardiovascular symptoms. |
Liver/kidney function | Exposure and dose limits vary with organ impairment. | Baseline/repeat testing; chronic-use label advises against severe hepatic impairment. |
Thyroid function | TSH changes occurred during chronic treatment. | Consider thyroid monitoring when clinically indicated in prolonged use. |
Managing side effects
Nausea, headache, fatigue or dizziness should be assessed in context, not automatically labelled minor. They overlap with dehydration, infection, electrolyte disturbance and glucocorticoid deficiency. A prescriber may adjust/hold treatment, treat symptoms or investigate the cause. Antiemetics themselves need QT and metabolism review.
Potassium replacement and mineralocorticoid-blocking treatment, when appropriate, are clinician-directed. Do not self-start high-dose potassium or spironolactone: kidney function, the reason for low potassium and other medicines influence safety.
If adrenal insufficiency is suspected, the product label directs immediate treatment interruption and glucocorticoids without delay. Higher glucocorticoid doses may be needed to overcome receptor blockade. This is an emergency-team task, not a home dose-adjustment protocol. Carry the drug name, dose, last-dose time and prescriber contact.
Seek urgent assessment for
Fainting, collapse, severe weakness, confusion or persistent vomiting.
Palpitations with dizziness, chest pain or new severe breathlessness.
Fever during marrow-suppressing treatment, using the oncology team's fever instructions.
Heavy or prolonged bleeding, or bleeding accompanied by light-headedness.
A severe or blistering rash, facial/throat swelling or breathing difficulty.
Tell emergency staff that mifepristone blocks glucocorticoid effects and persists after stopping. Do not delay urgent steroids or other lifesaving care while trying to preserve an experimental anticancer mechanism.
8. Safety and interaction issues
Mifepristone is both affected by drug-metabolising enzymes and capable of changing other medicines' exposure. Its receptor effects create additional interactions that are not solved by adjusting blood levels alone. A full pharmacist review should include prescription medicines, OTC agents, supplements and recently stopped drugs.
Medicine/situation | Issue and practical interpretation |
Dexamethasone, prednisone, methylprednisolone and other systemic glucocorticoids | Mifepristone antagonises their effects. This affects brain swelling, antiemesis, allergic reactions, autoimmune illness and checkpoint-toxicity rescue. KORLYM is contraindicated with lifesaving systemic corticosteroid use. |
Paclitaxel / nab-paclitaxel | Inhibition of CYP2C8/CYP3A4 can reduce clearance and increase exposure. The combination trials showed increased neutropenia. |
Other CYP3A-dependent anticancer agents | Exposure may rise; evaluate each targeted drug/endocrine partner against its current label rather than assuming a class-wide safe dose. |
Strong CYP3A inhibitors | Azole antifungals, clarithromycin and ritonavir-containing medicines can raise mifepristone exposure. Label-specific adjustments/limits exist for Cushing's use, not as an oncology dosing guide. |
CYP3A inducers | Rifampicin, carbamazepine, phenytoin, phenobarbital and St John's wort can lower exposure; the KORLYM label advises avoiding coadministration. |
QT-prolonging medicines | Some antiemetics, antibiotics and anticancer drugs add risk. Low potassium further increases concern. |
Warfarin / other anticoagulants | CYP2C9 effects can increase warfarin exposure; uterine bleeding adds a separate risk. Other anticoagulants require individual assessment. |
Diclofenac and other CYP2C9-metabolised NSAIDs | The KORLYM label warns of increased NSAID exposure through CYP2C8/2C9 inhibition. Diclofenac therefore needs review for exposure and bleeding/organ toxicity, not an assumption of a beneficial combination. |
Fentanyl, simvastatin/lovastatin, tacrolimus/sirolimus and selected narrow-range CYP3A drugs | Listed contraindications with KORLYM include these examples. Fentanyl is particularly relevant in cancer pain care. Do not abruptly stop analgesia: arrange an alternative/managed plan before treatment. |
2-DG | Both have reported QT concerns. This is a potential overlapping-risk issue, not evidence of anticancer synergy or a studied clinical pair. |
Metformin / other glucose-lowering treatment | Glucose needs and symptoms require review, especially with altered cortisol action, poor intake or organ impairment. No verified cancer efficacy claim for this pair is made here. |
Hormonal contraception | Effectiveness can be impaired. The chronic-use label specifies non-hormonal contraception during treatment and for one month after stopping; a combination protocol may require longer. |
Endometrial disease: an important distinction
The KORLYM label contraindicates use in people with unexplained vaginal bleeding, atypical endometrial hyperplasia or endometrial carcinoma. Laboratory work on endometrial cancer does not override this. Any investigational use in that setting requires a formal specialist/research framework addressing the conflict.
Avoid simplistic supplement rules
There is no verified blanket rule that every antioxidant should be stopped with mifepristone. Assess a product's actual interaction potential, dose and purpose. Conversely, “natural” does not establish safety; St John's wort is an explicit enzyme-induction concern.
9. International sourcing and access
Confirm the exact medicine
Mifepristone is not misoprostol.
Some reproductive-health products/package regimens contain both.
Misoprostol is not a routine component of the oncology research regimens described here. A combination pack must not be treated as an oncology prescription.
Relacorilant and onapristone are different drugs, not alternative brands of mifepristone. Results for a more selective GR modulator or another PR antagonist cannot be assigned to mifepristone.
Three separate questions
1. Is the intended prescribing/supply lawful in the treatment country?
2. Is the actual product a quality-assured human medicine?
3. Can safe, lawful supply and monitoring continue after travel?
Availability for reproductive healthcare or Cushing's syndrome does not automatically establish an oncology supply pathway. Regulations, dispensing conditions, cost and availability differ internationally and can change.
United States example
FDA information distinguishes 200 mg reproductive-health products covered by the mifepristone REMS from KORLYM 300 mg for selected Cushing's-related hyperglycaemia. These are different labelled indications and supply arrangements. Neither is a general cancer approval. Current federal/state requirements and off-label arrangements must be checked by the treating prescriber and pharmacy rather than inferred from a past trial or an online seller.
Australia example
TGA material identifies mifepristone/misoprostol within MS-2 Step reproductive-health products. A proposed indication under evaluation is not the same as an approved indication. This report has not verified a current Australian chronic-oncology product or supply pathway. An Australian prescriber/pharmacist should determine whether an appropriate registered product, lawful off-label arrangement or an unapproved-medicine pathway applies to the actual proposed product. Overseas prescriptions do not automatically solve local dispensing/import requirements.
International clinic and pharmacy checklist
Exact active ingredient, strength, manufacturer and single-agent versus combination packaging.
Legal prescribing/dispensing basis for the intended use and treatment duration.
Licensed pharmacy, batch/expiry traceability and appropriate storage.
Cancer-specific evidence and the intended role of each agent in a combination.
Full interaction review, especially steroids, opioids, CYP-dependent drugs and QT risks.
Potassium/ECG/blood-count and organ-function monitoring arrangements.
Emergency glucocorticoid-rescue documentation and cross-border handover.
Agreed review criteria, cost, continuity and stopping/holding arrangements.
No supplier or clinic is endorsed in this draft. A historic trial's named supplier is not evidence of current lawful access or product equivalence.
10. Connected working notes and evidence gaps
“Mifepristone can inhibit CYP2C9-related metabolism. Diclofenac exposure and toxicity may therefore increase; assess the pairing pharmacologically rather than assuming that distinct anticancer mechanisms establish compatibility.”
“Mifepristone and 2-DG have separate QT-related safety concerns. No verified clinical anticancer evidence for this pair is presented here; a proposed combination requires an ECG/electrolyte and interaction review.”
Sources and further reading
Human breast-cancer studies
Elía A et al. Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial. Clinical Cancer Research. 2023;29(5):866 onwards. Published online in 2022. Core biomarker-selected PR-directed study; short single-arm window design.
Chen N et al. A randomized phase II trial of nab-paclitaxel with or without mifepristone for advanced triple-negative breast cancer. Breast Cancer Research and Treatment. 2025;211:111–119. DOI: 10.1007/s10549-025-07626-5. Essential comparator evidence: no PFS benefit, more neutropenia, small sample.
https://link.springer.com/article/10.1007/s10549-025-07626-5
Stringer-Reasor EM et al. Carboplatin, gemcitabine, and mifepristone for advanced breast and recurrent/persistent epithelial ovarian cancer. Breast Cancer Research and Treatment. 2025;213:347–354. DOI: 10.1007/s10549-025-07783-7. Original phase I combination trial; activity, dose reductions and marrow toxicity.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12396977/
Steroid profile in patients with breast cancer and in mice treated with mifepristone. 2023. Supplementary endocrine context from the MIPRA programme; not an independent efficacy trial.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10762537/
Other human cancer evidence
Ji Y et al. Double-Blind Phase III Randomized Trial of the Antiprogestin Agent Mifepristone in the Treatment of Unresectable Meningioma: SWOG S9005. Journal of Clinical Oncology. 2015. DOI: 10.1200/JCO.2015.61.6490. Negative placebo-controlled trial despite biological rationale.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669593/
Taplin ME et al. A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones. BJU International. 2008;101:1084–1089. DOI: 10.1111/j.1464-410X.2008.07509.x. Limited activity and increased androgens; abstract verified through institutional publication record.
Check JH, Check DL, Wilson C. Good Quality 66.7% 5-year Overall Survival in Terminal Lung Cancer Patients Treated With Mifepristone. Anticancer Research. 2025;45:5785–5798. DOI: 10.21873/anticanres.17911. Six-patient case report/series, not a comparative trial.
https://pubmed.ncbi.nlm.nih.gov/41318113/
Check JH et al. Significant Palliative Benefits Following Therapy With Mifepristone for Advanced Treatment Resistant Small Cell Lung Cancer. Anticancer Research. 2024;44:659–664. DOI: 10.21873/anticanres.16855. Single-patient report, not independent confirmation of a population response rate.
https://pubmed.ncbi.nlm.nih.gov/38307551/
Rocereto TF et al. Phase II Study of Mifepristone (RU486) in Refractory Ovarian Cancer. Gynecologic Oncology. 2000;77:429–432. Identified historical monotherapy study; complete outcome extraction remains for a later revision.
https://www.sciencedirect.com/science/article/pii/S0090825800957895
Rocereto TF et al. A phase II evaluation of mifepristone in the treatment of recurrent or persistent epithelial ovarian, fallopian or primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecologic Oncology. 2010. Identified follow-up phase II study; do not infer efficacy from its registration or title.
https://www.sciencedirect.com/science/article/pii/S0090825809008907
Reviews, preclinical studies and prevention context
Mifepristone Repurposing in Treatment of High-Grade Gliomas. Frontiers in Oncology. 2021;11:606907. DOI: 10.3389/fonc.2021.606907. Core glioma anchor review; mechanisms and original references. Its trial statuses and broad safety statements are historical and should be read alongside labels and newer trials.
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.606907/full
Mifepristone Overcomes Tumor Resistance to Temozolomide Associated with DNA Damage Repair and Apoptosis in an Orthotopic Model of Glioblastoma. Cancers. 2019;11(1):16; published online December 2018. Animal-model study, not a human MGMT-resistance trial.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356343/
Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment. International Journal of Oncology. 2009;34:743–755. DOI: 10.3892/ijo_00000200. Cell-study rationale for sequencing/regrowth suppression.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2690705/
The potential role of mifepristone in breast cancer prevention. 2025. Viewpoint on prevention; do not equate prevention biomarkers with treatment of established metastatic cancer.
https://www.thelancet.com/journals/lanogw/article/PIIS3050-5038(25)00013-5/fulltext
Transcriptomic Profile of Breast Tissue of Premenopausal Women Following Mifepristone Treatment. 2024. Normal breast-tissue changes; prevention context rather than evidence of tumour response.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11277027/
Trial records and status context
ClinicalTrials.gov. Study of Pembrolizumab and Mifepristone in Patients With Advanced HER2-negative Breast Cancer. NCT03225547. Protocol, eligibility, steroid/radiation and interaction considerations. Registry design is not a final efficacy result.
https://clinicaltrials.gov/study/NCT03225547
National Cancer Institute. Pembrolizumab and Mifepristone in Treating Patients with Metastatic or Locally Advanced Breast Cancer. NCI-2018-00004. Listing retrieved as closed to accrual.
https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-00004
Premedication with steroids in breast cancer – supportive treatment … 2026. Secondary review used only for its report of trial-status/safety context; the full title and final outcome citation need bibliographic completion before publication.
https://pmc.ncbi.nlm.nih.gov/articles/PMC13233022/
Prescribing information and regulatory access
DailyMed / Corcept Therapeutics. KORLYM—mifepristone tablet: prescribing information. Record updated April 2024. Primary chronic-use safety, pharmacology, interactions and non-oncology dose information. Verify the current local product label.
US Food and Drug Administration. Information about Mifepristone for Medical Termination of Pregnancy Through Ten Weeks Gestation. Regulatory distinction for 200 mg products/REMS; not a cancer indication or a full current state-law guide.
Therapeutic Goods Administration. MS2-STEP MS Health Pty Ltd—prescription medicines under evaluation. Proposed reproductive-health indication; an under-evaluation page is not proof of approval or oncology access.
https://www.tga.gov.au/resources/prescription-medicines-under-evaluation/ms2-step-ms-health-pty-ltd