Thiotepa

ROC STATUS: Known human carcinogen since 1998

ALSO KNOWN AS: TESPA, triethylenethiophosphoramide, TSPA, thio-TEPA

RELATED CANCERS: Leukemia

DEFINITION: Thiotepa is a colorless or white crystalline solid that is odorless.

Exposure routes: Some cancer patients are exposed to thiotepa when it is used as a chemotherapy treatment. It is typically administered intravenously. It may be injected into muscle tissue, directly into a tumor, or through a catheter into a body cavity. Potential exposure by direct contact can occur to workers involved in the formulation, packaging, preparation, and administration of thiotepa for use in chemotherapy treatments.

Where found: Thiotepa is found at sites where it is manufactured, packaged, and supplied. It can be found at medical facilities, where it is prepared and administered during cancer treatments. During the 1970s, it was found in some polymeric flame retardants for cotton and some insecticides.

At risk: Patients who are treated with thiotepa for various cancers, including bladder cancer, ovarian cancer, breast cancer, bronchial cancer, mesotheliomas, and lymphomas, are at high risk. Workers at locations where thiotepa is manufactured, packaged, and supplied for chemotherapy treatments are at risk for contamination. Healthcare professionals who prepare and administer thiotepa for cancer therapy risk contamination.

ETIOLOGY AND SYMPTOMS OF ASSOCIATED CANCERS: Thiotepa is an alkylating agent that slows or stops the growth of cancer cells in the human body. It can induce deoxyribonucleic acid (DNA) damage, changes in chromosome structure or number, addition or deletion of chromosomes, and cell transformation. It can also control the accumulation of fluids in body cavities that result from various cancers. Side effects of thiotepa chemotherapy include low white and red blood cell counts, decrease in platelets, hair loss, mouth sores, loss of appetite, tightness of the throat, nausea and vomiting, hives, rash, bladder irritation, and painful urination.

History: Thiotepa was first used in cancer therapy treatment of lymphomas and malignant tumors in 1953. Between 1970 and 1978, a link was established between the secondary development of leukemia and exposure to thiotepa. In the Second Report on Carcinogens (RoC; 1981), it was listed as a highly probable human carcinogen. By the 1990s, it was produced only in Japan. In the Eighth Report on Carcinogens (1998), thiotepa was listed as a known human carcinogen. To a large extent, it has been replaced by nitrogen mustard gas derivatives for chemotherapy treatments. It is still used in combination with other chemotherapy drugs for lymphomas and for bladder, ovarian, breast, lung, and brain cancers. It may also be used in experimental high-dose chemotherapy treatment and hematopoietic stem cell transplantation.

Bibliography

“Thiotepa Injection.” MedlinePlus, 15 Mar. 2013, medlineplus.gov/druginfo/meds/a682821.html. Accessed 19 June 2024.

"Thiotepa - Pharmaceuticals." NCBI, www.ncbi.nlm.nih.gov/books/NBK304333. Accessed 19 June 2024.

“Thiotepa (Tepadina) - Cancer information.” Cancer Research UK, 23 Mar. 2022, www.cancerresearchuk.org/about-cancer/treatment/drugs/thiotepa. Accessed 19 June 2024.

United States. Dept. of Health and Human Services. Public Health Service. Natl. Toxicology Program. Report on Carcinogens. 13th ed., Research Triangle: Author, 2014. National Toxicology Program.