Thiotepa
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-THIOTEPA |
|---|---|
| Type | Drug |
| Aliases | TESPATSPATTTepadinaThioplexTriethylenethiophosphoramideТіотепа |
| Status | reviewed 2026-04-26 | pending_clinical_signoff |
| Diseases | DIS-PCNSL |
| Sources | SRC-NCCN-BCELL-2025 |
Drug Facts
| Class | alkylating_agent — polyfunctional ethyleneimine (aziridine class) |
|---|---|
| Mechanism | 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. |
| Typical dosing | 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. |
| Ukraine registered | True |
| NSZU reimbursed | True |
| Ukraine last verified | 2026-04-27 |
Warnings
- 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
Notes
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.
Used By
Regimens
REG-MATRIX- MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles