Severe early fluorouracil or capecitabine toxicity - mucositis, diarrhoea, neutropenia in the first cycle - is frequently dihydropyrimidine dehydrogenase deficiency, and the first cycle is where it kills people. The deficiency is present before treatment starts and is detectable.
Where DPYD genotyping or uracil measurement is available, do it before cycle one and reduce the starting dose for a heterozygous variant rather than starting full dose and reacting. Where it is not available, the substitute is not to skip the thought: ask about family history of severe chemotherapy reactions, and be quicker than usual to stop and investigate a patient whose first cycle produces disproportionate toxicity.
The corollary is dose intensity in the other direction. A patient who sails through cycle one with no toxicity at all may be underexposed, and the reflex to be pleased about it is how underdosing goes unnoticed for six cycles.
- Test DPYD or plasma uracil before the first fluoropyrimidine dose where available
- Reduce the starting dose for a heterozygous DPYD variant rather than treating and reacting
- Treat disproportionate first-cycle toxicity as a reason to stop and investigate, not to dose-reduce and continue
- Ask about family history of severe reactions to chemotherapy at consent
- Note the opposite problem: no toxicity at all across several cycles may mean underexposure
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