Table 3. [The DPWG Recommendations for Capecitabine/Fluorouracil...]. - Medical Genetics Summaries

DPYD gene activity score	Recommendation	Pharmacist text
Activity score 1.5	Start with 50% of the standard dose or avoid fluorouracil and capecitabine. After starting treatment, the dose should be adjusted based on toxicity and effectiveness. Tegafur is not an alternative, as this is also metabolized by DPD.	The gene variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the normal dose is an overdose
Activity score 1.0	Start with 50% of the standard dose or choose an alternative. Adjustment of the initial dose should be guided by toxicity and effectiveness. Tegafur is not an alternative, as this is also metabolized by DPD.	Genetic variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the normal dose is an overdose.
PHENO¹	It is not possible to recommend a dose adjustment for these individuals based on the genotype only. Determine the residual DPD activity in mononuclear cells from peripheral blood and adjust the initial dose based on phenotype and genotype or avoid fluorouracil and capecitabine. Tegafur is not an alternative, as this is also metabolized by DPD.	The gene variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the normal dose is an overdose.
Activity score 0	Avoid fluorouracil and capecitabine Tegafur is not an alternative, as this is also metabolized by DPD. If an alternative is not possible: determine the residual DPD activity in mononuclear cells from peripheral blood and adjust the initial dose accordingly. An individual with 0.5% of the normal DPD activity tolerated 0.8% of the standard dose (150 mg capecitabine every 5 days). An individual with undetectable DPD activity tolerated 0.43% of the standard dose (150 mg capecitabine every 5 days with every third dose skipped).	Genetic variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the standard dose is a more than 100-fold overdose.

DPYD gene activity score

Recommendation

Pharmacist text

Activity score 1.5

Start with 50% of the standard dose or avoid fluorouracil and capecitabine. After starting treatment, the dose should be adjusted based on toxicity and effectiveness.
Tegafur is not an alternative, as this is also metabolized by DPD.

The gene variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the normal dose is an overdose

Activity score 1.0

Start with 50% of the standard dose or choose an alternative.
Adjustment of the initial dose should be guided by toxicity and effectiveness.
Tegafur is not an alternative, as this is also metabolized by DPD.

Genetic variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the normal dose is an overdose.

PHENO¹

It is not possible to recommend a dose adjustment for these individuals based on the genotype only.
Determine the residual DPD activity in mononuclear cells from peripheral blood and adjust the initial dose based on phenotype and genotype or avoid fluorouracil and capecitabine. Tegafur is not an alternative, as this is also metabolized by DPD.

The gene variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the normal dose is an overdose.

Activity score 0

Avoid fluorouracil and capecitabine
Tegafur is not an alternative, as this is also metabolized by DPD.
If an alternative is not possible:
determine the residual DPD activity in mononuclear cells from peripheral blood and adjust the initial dose accordingly.
An individual with 0.5% of the normal DPD activity tolerated 0.8% of the standard dose (150 mg capecitabine every 5 days). An individual with undetectable DPD activity tolerated 0.43% of the standard dose (150 mg capecitabine every 5 days with every third dose skipped).

Genetic variation increases the risk of severe, potentially fatal toxicity. A reduced conversion of fluorouracil/capecitabine to inactive metabolites means that the standard dose is a more than 100-fold overdose.

From: Fluorouracil Therapy and DPYD Genotype

Medical Genetics Summaries [Internet].

Pratt VM, Scott SA, Pirmohamed M, et al., editors.

Bethesda (MD): National Center for Biotechnology Information (US); 2012-.

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