Thiotepa — Drug Monograph

Brand names: Tepadina

Drug class: Alkylating Agent

Mechanism of Action

Thiotepa (N,N′,N″-triethylenethiophosphoramide) is a polyfunctional ethyleneimine alkylating agent. Under physiologic conditions the aziridine (ethyleneimine) rings open to form reactive carbonium/ethyleneimonium intermediates that alkylate the N7 position of guanine, producing DNA interstrand and intrastrand crosslinks that block DNA replication and transcription. It is cell-cycle nonspecific. Its small size and high lipophilicity give it excellent tissue and blood-brain barrier penetration, achieving CSF concentrations approaching plasma levels — the basis for its use in CNS-directed and…

FDA Indications

• Adenocarcinoma of the breast (palliative)
• Adenocarcinoma of the ovary (palliative)
• Superficial papillary carcinoma of the urinary bladder (intravesical instillation)
• Controlling intracavitary effusions (malignant pleural, pericardial, or peritoneal effusions)

Common Side Effects

• Myelosuppression (neutropenia, thrombocytopenia, anemia) — dose-limiting
• Nausea and vomiting
• Mucositis/stomatitis (prominent at high doses)
• Skin hyperpigmentation and desquamation, especially in occluded/high-sweat areas (high-dose)
• Fatigue
• Fever
• Anorexia

Clinical Pearl

Thiotepa's defining property is its excellent CNS penetration — small, lipophilic, and largely un-ionized at physiologic pH, it crosses the blood-brain barrier to reach near-plasma CSF concentrations. This makes it a cornerstone of both the MATRix induction regimen for primary CNS lymphoma and thiotepa-based (e.g. thiotepa/busulfan or thiotepa/BCNU) conditioning before autologous stem cell transplant consolidation, where CNS coverage is essential. Because thiotepa is excreted in sweat and can…

Related Therapies & Mechanisms

• Carboplatin (Paraplatin) — Alkylating Agent · Breast
• Cisplatin (Platinol) — Alkylating Agent · Bladder
• Cyclophosphamide (Cytoxan) — Alkylating Agent · Breast
• Ifosfamide (Ifex) — Alkylating Agent · Bladder