Abstract
Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP- glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.
| Original language | English |
|---|---|
| Pages (from-to) | 158-165 |
| Number of pages | 8 |
| Journal | Journal of Chemotherapy |
| Volume | 20 |
| Issue number | 2 |
| Publication status | Published - Apr 2008 |
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Keywords
- APC: 7-ethyl-10-[4-N-(5-amino pentanoic acid)-1-piperidino]- carbonyloxycamptothecin
- CRC: Colorectal cancer
- hCE: Human carboxylesterases
- NPC: 7-ethyl-10-[4-(1-piperidino)-1-amino]- carbonyloxycamptothecin
- SN38: 7-ethyl-10-hydroxycamptothecin
ASJC Scopus subject areas
- Pharmacology (medical)
- Microbiology (medical)
- Medicine(all)
Cite this
UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity. / Biason, P.; Masier, S.; Toffoli, Giuseppe.
In: Journal of Chemotherapy, Vol. 20, No. 2, 04.2008, p. 158-165.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity
AU - Biason, P.
AU - Masier, S.
AU - Toffoli, Giuseppe
PY - 2008/4
Y1 - 2008/4
N2 - Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP- glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.
AB - Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP- glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.
KW - APC: 7-ethyl-10-[4-N-(5-amino pentanoic acid)-1-piperidino]- carbonyloxycamptothecin
KW - CRC: Colorectal cancer
KW - hCE: Human carboxylesterases
KW - NPC: 7-ethyl-10-[4-(1-piperidino)-1-amino]- carbonyloxycamptothecin
KW - SN38: 7-ethyl-10-hydroxycamptothecin
UR - http://www.scopus.com/inward/record.url?scp=44849107763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44849107763&partnerID=8YFLogxK
M3 - Article
C2 - 18467239
AN - SCOPUS:44849107763
VL - 20
SP - 158
EP - 165
JO - Journal of Chemotherapy
JF - Journal of Chemotherapy
SN - 1120-009X
IS - 2
ER -