A genotype-directed phase I–IV dose-finding study of irinotecan in combination with fluorouracil/leucovorin as first-line treatment in advanced colorectal cancer
2011

Irinotecan Dose Adjustment Based on Genetic Testing in Colorectal Cancer

Sample size: 94 publication Evidence: moderate

Author Information

Author(s): Marcuello E, Páez D, Paré L, Salazar J, Sebio A, del Rio E, Baiget M

Primary Institution: Universitat Autònoma de Barcelona

Hypothesis

Irinotecan dose individualisation based on UGT1A1 genotype will improve treatment tolerance and efficacy in advanced colorectal cancer.

Conclusion

The study found that the maximum tolerated dose of irinotecan is significantly higher for patients with certain UGT1A1 genotypes compared to the standard dose.

Supporting Evidence

  • The maximum tolerated dose of irinotecan was found to be higher for patients with UGT1A1 *1/*1 and *1/*28 genotypes.
  • Patients with the *28/*28 genotype had a maximum tolerated dose that was 30% lower than the standard dose.
  • Neutropenia and diarrhoea were the most common severe toxicities observed.

Takeaway

Doctors can give higher doses of a cancer drug called irinotecan to some patients based on their genes, which helps them tolerate the treatment better.

Methodology

Patients were treated with FOLFIRI and classified by UGT1A1 genotype to determine the maximum tolerated dose of irinotecan.

Limitations

The study did not include a pharmacokinetics analysis to describe the effect of different irinotecan doses on drug exposure.

Participant Demographics

{"median_age":63,"sex_distribution":{"male":61,"female":39},"ethnicity":"white"}

Statistical Information

P-Value

p<0.05

Confidence Interval

95%: 1.76–18.51

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/bjc.2011.206

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