Thiotepa
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | DRUG-THIOTEPA |
|---|---|
| Тип | Препарат |
| Синоніми | TESPATSPATTTepadinaThioplexTriethylenethiophosphoramideТіотепа |
| Статус | переглянуто 2026-04-26 | очікує клінічного підпису |
| Хвороби | DIS-PCNSL |
| Джерела | SRC-NCCN-BCELL-2025 |
Дані про препарат
| Клас | alkylating_agent — polyfunctional ethyleneimine (aziridine class) |
|---|---|
| Механізм дії | Polyfunctional alkylating agent: each of three ethyleneimine groups generates an aziridinium intermediate that alkylates DNA primarily at N7 of guanine, producing intra-strand and inter-strand cross-links → DNA replication arrest and apoptosis. Active metabolite TEPA (triethylenephosphoramide, formed by hepatic CYP3A4 / CYP2B6 desulfuration) contributes equally to cytotoxicity. Highly lipid-soluble — penetrates CNS readily (CSF levels ~100% of plasma), the basis of its central role in PCNSL induction (MATRix), CNS-relapse-risk lymphoma conditioning (TBC = thiotepa + busulfan + cyclophosphamide; TT-BCNU), and intrathecal use for leptomeningeal disease. |
| Типове дозування | PCNSL MATRix induction (Ferreri 2016): 30 mg/m² IV days 4-5 of cycle (4 cycles), with rituximab + HD-MTX 3.5 g/m² + cytarabine 2 g/m² q12h. Auto-SCT conditioning (TBC for CNS lymphoma): thiotepa 5 mg/kg IV q12h × 2 doses days -7 and -6, with busulfan + cyclophosphamide. Auto-SCT conditioning (TT-BCNU): thiotepa 250 mg/m² IV days -5 to -3 with carmustine 400 mg/m² day -6. Allo-SCT (haploidentical): thiotepa 5 mg/kg IV day -7 with TBI / busulfan / fludarabine. Intrathecal (rare): 1-10 mg per dose. |
| Зареєстровано в Україні | True |
| Відшкодовується НСЗУ | True |
| Остання перевірка для України | 2026-04-27 |
Застереження
- Severe myelosuppression — universal at conditioning doses; requires stem-cell rescue
- Hepatic veno-occlusive disease / sinusoidal obstruction syndrome at conditioning doses (especially with busulfan)
- Skin and mucosal toxicity — drug excreted in sweat; thorough skin washing required at high doses
Нотатки
In MATRix the thiotepa component is what enhances CNS penetration and drives the regimen's superior CR rate vs MTR (Ferreri IELSG32 trial, Lancet Haematol 2016). For CNS-relapse-risk lymphomas autoSCT, TBC (thiotepa + busulfan + cyclophosphamide) and TT-BCNU are preferred over BEAM (Soussain 2008; Cordoba/MSKCC retrospective). Drug is excreted in sweat — patient must shower BID and change linens during HD therapy to avoid contact dermatitis (caregivers also). Defibrotide prophylaxis considered for high-VOD-risk patients (prior abdominal RT, baseline hepatic dysfunction). Intrathecal use largely supplanted by IT-MTX + IT-cytarabine but retained in select pediatric protocols.
Де використовується
Regimens
REG-MATRIX- MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles