thiotepa
Meaning of thiotepa: An old alkylating drug that persists in use because it crosses into the brain and can be instilled into the bladder.
Definition of thiotepa
Thiotepa is an alkylating chemotherapy drug that attaches carbon groups to DNA and links the two strands together, so they cannot separate and the cell cannot divide. It is small and fat-soluble enough to enter the brain and the fluid around the spinal cord, which is unusual for a drug of this kind. It is given into a vein, into the bladder, or into the spinal fluid.
How does it stop a cell dividing?
By gluing DNA to itself. As an alkylating agent it transfers small carbon groups onto the bases of DNA, and because the molecule has more than one reactive arm it can bond to both strands at once. A cross-linked double helix cannot be pulled apart, and a cell that cannot separate its strands cannot copy them or divide. Cells dividing fastest are hit hardest, which is why the drug works against cancer and why bone marrow, gut lining and hair suffer alongside. The compound is a prodrug: the liver converts it into a second substance that is itself active, so the effect outlasts the parent drug in the blood.
Where is it given, and why there?
| Route | Purpose |
|---|---|
| Into a vein at high dose | Clearing marrow before a stem cell transplant |
| Into the bladder | Treating surface tumors of the bladder lining directly |
| Into the spinal fluid | Reaching cancer spread to the linings of the brain |
Its ability to cross into the brain is what has kept it in anticancer therapy while contemporaries fell out of use. Most chemotherapy is largely shut out of the nervous system, so a drug that gets in has a role in central nervous system lymphoma and in some childhood brain tumors, particularly within the intensive regimens used before a transplant.
What are its main hazards?
Suppression of the bone marrow limits the dose and is expected rather than exceptional, bringing low blood counts, infection risk and bleeding. Mouth and gut lining ulcerate. A peculiarity appears at high dose: the drug and its active product leave the body partly in sweat, so skin becomes inflamed and darkened where sweat gathers, in the armpits, the groin and under dressings, and washing frequently is part of routine care during those regimens. Like other alkylating agents it damages DNA in healthy cells too, and a later blood cancer is a recognized long-term risk.
Also known as
Used in a sentence
Thiotepa was included in the conditioning regimen before the transplant.
Good to know
Thiotepa and its active breakdown product are excreted partly in sweat, so at the high doses used before a stem cell transplant the skin can become inflamed and darkened where sweat collects, particularly in folds and under dressings.