UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study

2008

UGT1A1*28 Genotype and Irinotecan Dosage in Colorectal Cancer

Sample size: 218 publication 10 minutes Evidence: moderate

Author Information

Author(s): Kweekel D M, Gelderblom H, Van der Straaten T, Antonini N F, Punt C J A, Guchelaar H-J

Primary Institution: Leiden University Medical Center

Hypothesis

The study investigates the associations between UGT1A1*28 genotype and response rates, febrile neutropenia, and dose intensity in patients with metastatic colorectal cancer treated with irinotecan.

Conclusion

TA7/TA7 patients have a higher incidence of febrile neutropenia upon irinotecan treatment but can receive similar doses and number of cycles compared to other genotypes.

Supporting Evidence

TA7 homozygotes receiving irinotecan combination therapy had a higher incidence of febrile neutropenia (18.2%) compared to TA6/TA6 (1.5%) and TA6/TA7 (6.5%).
TA7 heterozygotes receiving irinotecan monotherapy also suffered more febrile neutropenia (19.4%) compared to TA6/TA6 (2.2%).
Response rates among genotypes were not significantly different for both regimens.
TA7 homozygotes did not receive a lower median irinotecan dose or number of cycles compared to other genotypes.

Takeaway

Some people have a gene that makes them more likely to get sick from a cancer medicine called irinotecan, but they can still take the same amount of medicine as others.

Methodology

Blood samples were obtained from patients enrolled in a multicentre phase III trial, and UGT1A1*28 genotype was determined in patients receiving irinotecan.