Advanced and metastatic adrenocortical carcinoma: the decisions you may face
5 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
All patients
Mitotane from diagnosis with glucocorticoid replacement; adrenal enzyme inhibitors (metyrapone, osilodrostat, ketoconazole) for cortisol excess; thromboprophylaxis and infection vigilance.
A relative of the insecticide DDT that is the only drug specific to adrenal cortex cancer; it needs blood-level monitoring and permanent steroid replacement.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Is Mitotane the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?Why: A single standard does not mean a single choice; timing and trials are decisions too.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (ESE/ENSAT guideline on adrenocortical carcinoma 2018), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (all patients), which of the standard options do you recommend and why?Why: Guideline options include: Mitotane from diagnosis with glucocorticoid replacement; adrenal enzyme inhibitors (metyrapone, osilodrostat, ketoconazole) for cortisol excess; thromboprophylaxis and infection vigilance.
- Am I a candidate for Mitotane, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Low-burden, indolent disease
Mitotane alone, with resection, thermal ablation or stereotactic radiotherapy of limited metastases.
A relative of the insecticide DDT that is the only drug specific to adrenal cortex cancer; it needs blood-level monitoring and permanent steroid replacement.
Thermal ablation kills a tumour with heat or cold delivered through a needle, with no incision required.
- Outpatient, repeatable
- Preserves organ function
Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.
- Ablative doses with minimal recovery
- Outpatient
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Size limit ~3 cm
- Heat-sink near vessels
- Size and location limits
- Late toxicity near central airways
- Between Mitotane, Thermal ablation (RFA, microwave, cryo) and SBRT / SABR (stereotactic radiotherapy), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (ESE/ENSAT guideline on adrenocortical carcinoma 2018), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (low-burden, indolent disease), which of the standard options do you recommend and why?Why: Guideline options include: Mitotane alone, with resection, thermal ablation or stereotactic radiotherapy of limited metastases.
- Am I a candidate for Mitotane, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
High-burden or progressive disease, first line
Etoposide, doxorubicin and cisplatin with mitotane (EDP-M, FIRM-ACT).
Etoposide is a chemotherapy from the mayapple plant, essential to curing testicular cancer (BEP), treating small-cell lung cancer, lymphomas, childhood sarcomas and leukaemias, and used in transplant conditioning.
The red chemotherapy drug from a soil bacterium that is still the backbone of treatment for sarcoma, lymphoma and breast cancer, limited by cumulative heart damage.
Cisplatin is the original platinum chemotherapy, discovered by accident in 1965; it cures testicular cancer and makes radiation work better in cervical and head and neck cancer.
A relative of the insecticide DDT that is the only drug specific to adrenal cortex cancer; it needs blood-level monitoring and permanent steroid replacement.
Cytotoxic chemotherapy drugs (platinums, antimetabolites, microtubule agents and topoisomerase inhibitors) kill rapidly dividing cells by damaging DNA or the mitotic spindle. They still cure testicular cancer, lymphoma and leukaemia, and they are the warhead inside antibody-drug conjugates, but a narrow margin between effective and toxic doses is their limitation.
- Curative in several cancers
- Cheap, generic
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Reduce to 75% for CrCl 15-50.
- Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
- Reduce by 50% for bilirubin 20-50 µmol/L and 75% for 50-85 µmol/L.
- Dose reduce or avoid for CrCl below 60 (carboplatin is the alternative).
- Narrow therapeutic index
- Resistance via efflux pumps and DNA repair
- Between Etoposide, Doxorubicin, Cisplatin and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (ESE/ENSAT guideline on adrenocortical carcinoma 2018), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (high-burden or progressive disease, first line), which of the standard options do you recommend and why?Why: Guideline options include: Etoposide, doxorubicin and cisplatin with mitotane (EDP-M, FIRM-ACT).
- Am I a candidate for Etoposide, Doxorubicin, Cisplatin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
After EDP-M
Gemcitabine with capecitabine; cabozantinib; pembrolizumab, especially for mismatch-repair-deficient tumours; streptozocin-mitotane; clinical trials.
A versatile chemotherapy used in pancreatic, bladder, lung, ovarian, breast and biliary cancers, in nasopharyngeal cancer, and as a bladder instillation.
Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer.
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.
- Durable, sometimes curative responses
- Broad applicability
Pills that block the specific enzyme a cancer relies on. Imatinib in 2001 proved a cancer could be switched off by design.
- Oral, outpatient
- Dramatic responses in oncogene-addicted cancers
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Tablets: take on an empty stomach (no food 2 hours before or 1 hour after). Avoid grapefruit.
- Reduce to 40 mg daily in moderate impairment; avoid in severe.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Most patients do not respond
- Autoimmune toxicity
- Biomarkers are imperfect
- Near-universal resistance in metastatic disease
- Off-target toxicities
- Between Gemcitabine, Capecitabine, Cabozantinib and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (ESE/ENSAT guideline on adrenocortical carcinoma 2018), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (after edp-m), which of the standard options do you recommend and why?Why: Guideline options include: Gemcitabine with capecitabine; cabozantinib; pembrolizumab, especially for mismatch-repair-deficient tumours; streptozocin-mitotane; clinical trials.
- Am I a candidate for Gemcitabine, Capecitabine, Cabozantinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Trials
Relacorilant with checkpoint inhibition for cortisol-secreting tumours; cabozantinib with immunotherapy; radiolabelled CYP11B tracers.
A first-in-class drug that blocks cortisol signalling in tumour cells, approved in 2026 for platinum-resistant ovarian cancer with chemotherapy.
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Tablets: take on an empty stomach (no food 2 hours before or 1 hour after). Avoid grapefruit.
- Reduce to 40 mg daily in moderate impairment; avoid in severe.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Relacorilant, Cabozantinib and Pembrolizumab, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (ESE/ENSAT guideline on adrenocortical carcinoma 2018), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (trials), which of the standard options do you recommend and why?Why: Guideline options include: Relacorilant with checkpoint inhibition for cortisol-secreting tumours; cabozantinib with immunotherapy; radiolabelled CYP11B tracers.
- Am I a candidate for Relacorilant, Cabozantinib, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.