Tiotepa

Tiotepa, commonly known as thiotepa, is a synthetic cytotoxic chemotherapy agent used to treat various cancers. It is a bifunctional alkylating agent of the phosphoramide mustard family. By alkylating DNA, thiotepa creates cross-links between DNA strands, inhibiting replication and transcription and leading to cell death. Some cross-linking of RNA may also contribute to its cytotoxic effects.

Indications and administration: Thiotepa is used systemically for certain solid tumors and hematologic malignancies, and intravesically for non-muscle invasive bladder cancer. It is also employed as part of conditioning regimens before hematopoietic stem cell transplantation to suppress the patient’s bone marrow. Dosing and route depend on the regimen; intravenous administration is common in systemic therapy, while intravesical instillation is used for bladder cancer.

Pharmacokinetics and interactions: Thiotepa is rapidly distributed and largely eliminated by the kidneys, with hepatic metabolism contributing to clearance. It is usually given in combination with other cytotoxic agents. Potential drug interactions include additive bone marrow suppression with other myelosuppressive drugs.

Adverse effects and safety: The principal dose-limiting toxicity is myelosuppression, with neutropenia and thrombocytopenia. Other frequent adverse effects include mucositis, nausea and vomiting, diarrhea, fatigue, alopecia, and skin rash. Hepatic and pulmonary toxicity can occur, and the drug is teratogenic; handling requires caution as it is a vesicant.

History and status: Thiotepa has been in clinical use since the mid-20th century and remains an option in selected regimens and specialized settings.