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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: September 12, 2020.



Thiotepa is an intravenously or locally applied alkylating agent which is currently used in the therapy of breast, ovarian and bladder cancer. Thiotepa therapy has been associated with low rates of serum enzyme elevations during therapy and rare instances of acute, clinically apparent injury.


Thiotepa (thye' oh tep' a) is an ethylenimine similar in structure and activity to altretamine and is believed to act as an alkylating agent. The alkylating agents act by causing modification and cross linking of DNA, thus inhibiting DNA, RNA and protein synthesis and causing programmed cell death (apoptosis) in rapidly dividing cells. Thiotepa was approved for use in the United States in 1959. Current indications include ovarian and breast cancer and Hodgkin disease. Thiotepa is also administered locally for bladder cancer, neoplastic effusions and malignant meningeal neoplasms. Thiotepa is available generically in vials of 15 mg. The recommended dose varies by indications, route of administration, and body weight. Thiotepa shares common side effects with other alkylating agents such as nausea, vomiting, diarrhea, alopecia, mucositis, bone marrow suppression, rash and hypersensitivity reactions. Uncommon but potentially serious adverse events include severe myelosuppression, severe infections, sepsis, bleeding, and embryo-fetal toxicity.


Thiotepa is associated with an appreciable rate of serum enzyme elevations during therapy, but these are generally mild and self-limited, not requiring dose adjustment. Rare instances of clinically apparent acute liver injury attributed to thiotepa have been reported, particularly with high doses. In most instances, thiotepa was administered in combination with other agents known to cause liver injury and the specific role of thiotepa was not clear.

Thiotepa is often used in combination with other alkylating agents in conditioning regimens for bone marrow ablation in preparation for hematopoietic cell transplantation and as such has been linked to instances of sinusoidal obstruction syndrome. Onset of sinusoidal obstruction syndrome is usually within 1 to 3 weeks of myeloablative or high dose therapy and is characterized by the sudden development of abdominal pain, hepatomegaly, weight gain and ascites followed by jaundice. The pattern of serum enzyme elevations is usually hepatocellular, with marked increases in serum aminotransferase and lactic dehydrogenase levels and minimal increase in alkaline phosphatase. In severe instances, there are elevations in prothrombin time and progressive hepatic failure. Immunoallergic and autoimmune features are uncommon. The fatality rate is high. Liver biopsy shows centrolobular necrosis and congestion with occlusion of small veins and red cells in sinusoids.

Likelihood score: D (possible, rare cause of clinically apparent liver injury).

Mechanism of Injury

The potential mechanism of hepatotoxicity from thiotepa is probably similar to that of other alkylating agents, a direct cytotoxic injury to rapidly dividing cells. High doses are likely to injure other cells such as sinusoidal endothelial cells and hepatocytes. The cause of the idiosyncratic liver injury associated with thiotepa is not known.

Outcome and Management

Liver injury is not uncommon with high doses of thiotepa. The severity of injury in reported cases has generally been mild-to-moderate and self-limited in course, although fatalities attributed to hepatotoxicity have been reported. The sinusoidal obstruction syndrome associated with thiotepa and other alkylating agents can be severe and lead to acute liver failure. There have been no instances of chronic hepatitis or vanishing bile duct syndrome definitely linked to thiotepa therapy. In situations of acute liver injury after thiotepa use, rechallenge should be avoided.

Drug Class: Antineoplastic Agents, Alkylating Agents



Thiotepa – Generic, Thioplex®


Antineoplastic Agents, Alkylating Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Thiotepa 52-24-4 C6-H12-N3-P-S image 134972906 in the ncbi pubchem database


References updated: 12 September, 2020

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