irinotecan
Meaning of irinotecan: A chemotherapy drug best known for treating advanced bowel cancer, and for the severe diarrhea that can follow a dose.
Definition of irinotecan
Irinotecan is a chemotherapy drug given by drip, used mainly for cancer of the colon and rectum and for several other advanced cancers. It is inactive as given and the body converts it into a far more potent form. That active form jams an enzyme the cell needs to unwind its DNA before dividing, so the strands break and the dividing cell dies.
How does it kill a cancer cell?
DNA is wound tightly, and a cell cannot copy it without first relieving that tension. An enzyme called topoisomerase I does the job by nicking one strand, letting it swivel, then sealing it again. Irinotecan is a camptothecin derivative, and its active form binds the enzyme at the moment the strand is cut. The nick is never resealed. When the copying machinery reaches that point the break becomes permanent, and cells that divide fastest run into it first.
What is it used for?
Its established role is in advanced cancer of the bowel, where it is usually combined rather than given alone.
| Setting | How it is used |
|---|---|
| Advanced colorectal cancer | Combined with fluorouracil and folinic acid |
| Disease that returned after other drugs | Sometimes given on its own |
| Small cell lung cancer | Combined with a platinum drug |
| Pancreatic cancer | A liposomal form, packaged in fat bubbles |
Why is diarrhea such a problem with it?
Two separate kinds occur, and they behave differently. The early kind starts during or soon after the infusion and comes with cramping, watering eyes and sweating, because the drug briefly mimics a nerve signal that speeds the gut. The late kind appears days afterward and reflects direct damage to the lining of the bowel. The late form is the more dangerous, since fluid loss and low white cell counts can arrive together.
Why do people differ so much in what they tolerate?
The liver disposes of the active form by attaching a sugar to it, using an enzyme called UGT1A1. Some people inherit a version of the gene that works slowly, so the active drug lingers and the marrow and gut take a heavier hit. Testing for that variant is available, and the drug label reflects it. Low white cell counts and hair loss are common regardless.
Also known as
Used in a sentence
The regimen combined irinotecan with fluorouracil and folinic acid for metastatic colorectal cancer.
Good to know
Two distinct diarrhea patterns follow irinotecan, an early one driven by nerve stimulation and a late one from bowel lining damage, and inherited slow UGT1A1 activity raises the risk of severe marrow and gut toxicity.