Mitotane
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | DRUG-MITOTANE |
|---|---|
| Art | Arzneimittel |
| Aliase | LysodrenMitotane Esteveo,p'-DDDo.p.-DichlordiphenyldichlorethanМітотан |
| Status | reviewed 2026-07-11 | pending_clinical_signoff |
| Erkrankungen | DIS-ADRENOCORTICAL-CARCINOMA |
| Quellen | SRC-ADIUVO-TERZOLO-2023 SRC-ENSAT-ACC-2018 SRC-ESMO-ACC-2020 SRC-FIRM-ACT-FASSNACHT-2012 |
Drug Facts
| Klasse | Adrenolytisches zytotoxisches Mittel (DDT/o,p'-DDD-Derivat) — das einzige ACC-spezifische zugelassene zytotoxische Arzneimittel |
|---|---|
| Verfahren | Mitotane is a chlorinated hydrocarbon derivative of the insecticide DDT with selective adrenolytic activity. It accumulates in adrenocortical cells and is metabolized (partly CYP11B1-dependent) to a reactive acyl chloride metabolite that covalently binds mitochondrial and other cellular proteins, producing structural mitochondrial damage and direct cytotoxic necrosis of both normal and malignant adrenocortical tissue (zona fasciculata/reticularis predominantly). It also inhibits several steroidogenic enzymes (side-chain cleavage/CYP11A1, 3-beta-HSD, 11-beta- hydroxylase/CYP11B1) and is a potent, durable inducer of hepatic CYP3A4, which increases cortisol clearance and reduces exposure of many co-administered CYP3A4-metabolized drugs. The adrenolytic effect is not tumor-selective: essentially all patients develop drug-induced adrenal insufficiency and require glucocorticoid (+/- mineralo... |
| Typische Dosierung | Oral, 500 mg scored tablets. Initiated at 2-3 g/day PO in divided doses (higher starting doses of 4-6 g/day may be used when rapid disease control is urgent), taken with fatty meals to enhance absorption. Dose is increased progressively — typically at ~2-week intervals under standard conditions, or as often as weekly if expedited control is needed — guided by tolerability and mitotane blood level, toward a target therapeutic blood level of 14-20 mg/L (levels above 20 mg/L risk toxicity without additional antitumor benefit). Blood-level monitoring is required after each dose adjustment and at frequent intervals (e.g. every 2 weeks) during titration, then monthly at a stable maintenance dose,... |
| Ukraine registriert | Falsch |
| NSZU erstattet | Falsch |
| Ukraine zuletzt überprüft | 2026-07-11 |
Warnungen
- Adrenal insufficiency — mitotane is adrenolytic to both normal and malignant adrenocortical tissue; essentially all patients (100% with non-functional tumors, ~75% with functional tumors per EU SmPC) develop adrenal insufficiency and require glucocorticoid (+/- mineralocorticoid) replacement; unrecognized adrenal crisis during intercurrent illness, trauma, or surgery can be fatal.
- ZNS-Toxizität bei supratherapeutischen Blutspiegeln (> 20 mg/L) — Lethargie, Schwindel, Schwindel, Ataxie, Verwirrtheit; verwenden Sie Blutspiegelüberwachung, um innerhalb des 14-20 mg/L therapeutischen Fensters zu bleiben.
- Embryo-fetale Toxizität — kontraindiziert in der Schwangerschaft; wirksame Verhütung während und nach der Behandlung erforderlich, wenn das Medikament sehr lange Halbwertszeit.
Anmerkungen
STUB pending clinical co-lead sign-off (CHARTER §6.1). The only FDA/EMA-approved adrenal-cortex-specific cytotoxic agent; used as (1) adjuvant monotherapy after resection in high-recurrence-risk stage I-III ACC, and (2) continuously alongside EDP chemotherapy (etoposide + doxorubicin + cisplatin) in advanced/metastatic disease per the FIRM-ACT trial (Fassnacht 2012, NEJM). Dosing, titration cadence, target blood level (14-20 mg/L), and adrenal-insufficiency incidence figures are sourced from the EU SmPC for Mitotane Esteve 500 mg tablets (medicines.org.uk/emc/product/101074) — verify against institutional protocol and the primary ENSAT/ESMO guideline text before clinical use. The randomized ADIUVO trial (Terzolo 2023) found no significant benefit from adjuvant mitotane in a lower/intermediate-recurrence-risk resected population (stage I-III, R0, Ki-67 <=10%), so this KB restricts the adjuvant-mitotane Indication (IND-ACC-1L-RESECTION-MITOTANE) to a higher-recurrence-risk subgroup — see that Indication and RF-ACC-HIGH-RECURRENCE-RISK-BIOLOGY for detail.
Verwendet von
Therapieschema
REG-EDP-M-ACC- EDP-M (etoposide + Doxorubicin + cisplatin + mitotane) — FIRM-ACT DosierungREG-MITOTANE-ADJUVANT-ACC- Mitotane adjuvante Monotherapie (ACC)