thiotepa
Overview
Thiotepa (triethylenethiophosphoramide) is a polyfunctional alkylating agent that forms DNA interstrand cross-links via its aziridine rings. It penetrates the blood-brain barrier effectively, making it particularly useful in high-dose chemotherapy (HDC) conditioning regimens for central nervous system tumors. It is used in myeloablative conditioning prior to autologous or allogeneic stem-cell transplantation, often combined with busulfan.
Evidence in the corpus
- Component of the myeloablative high-dose chemotherapy (HDC) conditioning in a phase II trial (NCT00588523) for newly diagnosed 1p/19q-codeleted anaplastic oligodendroglioma (ODG3): thiotepa 250 mg/m²/day IV × 3 days (days −8 to −6) immediately preceded busulfan 3.2 mg/kg/day IV × 3 days (days −5 to −3) and PBSC reinfusion on day 0. Among 21 transplanted patients, there were no toxic deaths; median neutrophil engraftment was 9 days (range 8–12) and platelet engraftment 12 days (range 9–18). The 5-year OS in transplanted patients was 100% at median follow-up 66 months. PMID:28472509
- In an exploratory cross-trial comparison, the thiotepa/busulfan + ASCT backbone was shared between the TMZ-induction and prior PCV-induction cohorts; TMZ induction was non-inferior to PCV induction for OS (HR 3.38 favoring TMZ, P=0.005), validating this HDC conditioning as an effective platform regardless of induction regimen. PMID:28472509
Resistance mechanisms
- Not specifically reported in the corpus.
Cancer types (linked)
Sources
- PMID:28472509 — Thomas et al. 2017, J Clin Oncol. Phase II NCT00588523; thiotepa 250 mg/m²/day × 3 as HDC conditioning in 1p/19q-codeleted anaplastic oligodendroglioma; no toxic deaths; 5-year OS 100% in transplanted patients.
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