topotecan
Meaning of topotecan: A chemotherapy drug that jams the enzyme cells rely on to untangle DNA while they are copying it.
Definition of topotecan
Topotecan is a chemotherapy drug given for small cell lung cancer, for ovarian cancer that has returned after earlier treatment, and for cervical cancer. It belongs to a group called topoisomerase I inhibitors, derived from a compound found in the bark of a tree native to China. It traps the enzyme that relieves twisting in DNA, leaving breaks a dividing cell cannot repair.
How does it work?
DNA is a twisted double strand, and copying it means pulling the two strands apart. That pulling winds the DNA ahead of the copying machinery ever tighter, in the way twisting one end of a rope tightens the rest. Topoisomerase I solves this by cutting one strand, letting the tension unwind, and sealing the cut again. Topotecan binds at the moment the strand is cut and prevents the resealing step. The copying machinery then runs into an unrepaired break, the break becomes a full double-strand break, and the cell triggers its own death. Cells that are not dividing are far less affected, which is why fast-renewing tissue bears the brunt.
What is it used for?
| Disease | Setting |
|---|---|
| Small cell lung cancer | After earlier chemotherapy has stopped working |
| Ovarian cancer | Disease returning after platinum-based treatment |
| Cervical cancer | Advanced disease, combined with cisplatin |
How is it given and what follows?
It is given as a short infusion on consecutive days, with cycles repeated after a gap, and a capsule form exists for some uses. The dominant effect is on the bone marrow: neutrophils and platelets fall, reaching their lowest point about a week or so after treatment before recovering, which brings a risk of infection and of bruising or bleeding. Kidney function influences how quickly the drug is cleared, so it is checked before treatment. Fatigue, nausea, diarrhea and hair loss are common. Because it is a topoisomerase inhibitor acting on the same enzyme as irinotecan, the two are not combined.
Also known as
Used in a sentence
Second-line treatment with topotecan was started following relapse.
Good to know
Topotecan acts on topoisomerase I, and its main dose-limiting effect is suppression of the bone marrow, with the lowest blood counts appearing about a week after treatment.