Anticancer drugs: fluorouracil toxicity: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · Anticancer drugs: fluorouracil toxicity

Sample item

A 58-year-old man with colon cancer develops severe mucositis, profuse diarrhoea and profound neutropenia one week after his first cycle of fluorouracil at standard dose. Which underlying defect is most likely?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. Dihydropyrimidine dehydrogenase deficiency

More than 80 percent of fluorouracil is normally inactivated by dihydropyrimidine dehydrogenase (DPD). Patients with variants in the DPYD gene have markedly reduced clearance, so standard doses can cause life-threatening mucositis, diarrhoea and myelosuppression. Pre-treatment testing is increasingly advised, and capecitabine is affected similarly.

Option by option

  • A. Thiopurine methyltransferase deficiency

    TPMT deficiency predisposes to azathioprine and mercaptopurine toxicity.

  • B. UGT1A1 polymorphism

    UGT1A1 variants increase irinotecan toxicity.

  • C. Glucose-6-phosphate dehydrogenase deficiency

    G6PD deficiency causes haemolysis with oxidant drugs, not this toxicity pattern.

  • D. Dihydropyrimidine dehydrogenase deficiency (correct)

    Correct. Reduced DPD activity leads to fluorouracil accumulation and severe toxicity.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, Dihydropyrimidine dehydrogenase deficiency. More than 80 percent of fluorouracil is normally inactivated by dihydropyrimidine dehydrogenase (DPD).

Why is "Thiopurine methyltransferase deficiency" not the answer?

TPMT deficiency predisposes to azathioprine and mercaptopurine toxicity.

Why is "UGT1A1 polymorphism" not the answer?

UGT1A1 variants increase irinotecan toxicity.

Why is "Glucose-6-phosphate dehydrogenase deficiency" not the answer?

G6PD deficiency causes haemolysis with oxidant drugs, not this toxicity pattern.

What concept does this question test?

It tests Anticancer drugs: fluorouracil toxicity in Pharmacology. Patients with variants in the DPYD gene have markedly reduced clearance, so standard doses can cause life-threatening mucositis, diarrhoea and myelosuppression. Pre-treatment testing is increasingly advised, and capecitabine is affected similarly.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Anticancer drugs: fluorouracil toxicity?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.