Some of the most widely used chemotherapy drugs are cleared from the body by enzymes that a small number of people are born with less of. If you were born with less of one of these enzymes, a standard dose can act like an overdose, and the reaction can be severe or fatal. A simple test before treatment shows whether this is a concern. If it is, your dose may need to be lowered or the drug changed.
The two that matter most in solid tumors are DPYD and UGT1A1. DPYD controls how your body clears fluorouracil and capecitabine, the backbone of treatment for colorectal, stomach, pancreatic and some breast cancers. UGT1A1 controls how your body clears irinotecan, used in colorectal and pancreatic regimens. The FDA labeling for fluorouracil and capecitabine now tells doctors to consider DPYD testing before treatment begins, and the irinotecan labeling describes a lower starting dose for people who carry reduced-function UGT1A1.
In blood cancers the genes are different. TPMT and NUDT15 affect thiopurines such as mercaptopurine and azathioprine, used in the long maintenance phase of acute lymphoblastic leukemia, where reduced function can cause life-threatening drops in blood counts. G6PD affects rasburicase, given for tumor lysis syndrome, which carries a boxed warning for severe red blood cell destruction. None of the blood cancer panels listed on this site report any of these, so they have to be requested separately.
Timing is the whole point. These are inherited differences you have had since birth, not changes in the tumor, so the result does not expire and one test lasts a lifetime. It is only useful if it comes back before the first dose. Results usually take about a week, and the guidelines describe specific dose reductions rather than stopping treatment, so for most people this is an adjustment, not a closed door.
Because the result is inherited, a reduced-function result can also matter to parents, siblings and children who may one day need the same drugs. If yours comes back abnormal, ask whether it is worth mentioning to close relatives.
For Example
A woman about to start capecitabine for colon cancer is tested first, and turns out to carry one reduced-function copy of DPYD. Her oncologist starts her at half the standard dose and raises it carefully based on how she tolerates it. Without the test, the standard dose would likely have sent her to the hospital with severe mouth sores, diarrhea and a collapse in white blood cell counts.
A man starting a FOLFIRINOX regimen for pancreatic cancer has UGT1A1 testing and is found to clear irinotecan poorly. His team lowers the irinotecan component from the start, rather than discovering the problem after a hospitalization in the first cycle.
Questions To Ask Your Oncologist
- For solid tumors, does my treatment plan include fluorouracil, capecitabine or irinotecan? If so, can DPYD and UGT1A1 be tested before my first dose?
- For blood cancers, does my treatment plan include mercaptopurine, azathioprine or rasburicase? If so, can TPMT, NUDT15 and G6PD be tested before my first dose?
- If a problem is identified, would you lower the dose or change the drug?