Table 3. [RNPGx (2017) Recommendations for Irinotecan and UGT1A1 Genotype.]. - Medical Genetics Summaries

Dose of irinotecan	Recommendation
low doses (<180 mg/m²/week)	Presence of the UGT1A128* allele is not a major risk factor (little difference in risk of hematological or digestive toxicity irrespective of the genotype)
180—230 mg/m² spaced by 2—3-week intervals	Patients who are homozygous for the UGT1A128* allele have a higher risk of hematological and/or digestive toxicity than patients who are heterozygous or non-carriers. For these 28/28 patients, a 25-30% dose reduction is recommended, especially if the patient presents other risk factors for toxicity. Dose can be adjusted for subsequent cycles depending on the tolerance.
240 mg/m² or higher spaced by 2—3-week intervals	Homozygous UGT1A128* patients have a greatly increased risk of hematological toxicity (neutropenia) compared with other genotypes, contraindicating administration at this higher dose and leading to discussion of a standard dose depending on the associated risk factors. Administration of an intensive dose (240 mg/m²) is recommended only for 1/1 patients, or for 1/28 patients who have no other risk factors and who benefit from intensive surveillance.

Dose of irinotecan

Recommendation

low doses
(<180 mg/m²/week)

Presence of the UGT1A1*28 allele is not a major risk factor (little difference in risk of hematological or digestive toxicity irrespective of the genotype)

180—230 mg/m² spaced by 2—3-week intervals

Patients who are homozygous for the UGT1A1*28 allele have a higher risk of hematological and/or digestive toxicity than patients who are heterozygous or non-carriers.
For these *28/*28 patients, a 25-30% dose reduction is recommended, especially if the patient presents other risk factors for toxicity.
Dose can be adjusted for subsequent cycles depending on the tolerance.

240 mg/m² or higher spaced by 2—3-week intervals

Homozygous UGT1A1*28 patients have a greatly increased risk of hematological toxicity (neutropenia) compared with other genotypes, contraindicating administration at this higher dose and leading to discussion of a standard dose depending on the associated risk factors.
Administration of an intensive dose (240 mg/m²) is recommended only for *1/*1 patients, or for *1/*28 patients who have no other risk factors and who benefit from intensive surveillance.

From: Irinotecan Therapy and UGT1A1 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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