Biomedical Engineering Reference
In-Depth Information
research. Polymorphisms within the drug-metabolizing enzyme
UGT1A1, namely the
variant, is now recognized as a
known marker of irinotecan toxicity 3,46]. Specifically, patients with
this allele have a 70% reduction in enzyme activity and thus clear
irinotecan less quickly from their body than the rest of the population
[8,24]. They effectively receive a greater exposure to the drug from
the same dose and as a consequence are at higher risk of considerable
side effects such as neutropenia and diarrhea [3-6,9,12,13]. In light of
this information, the labeling of irinotecan was recently changed and
now includes a warning of greater irinotecan toxicity in patients with
the
UGT1A1*28
genotype [8-10,12,14-16, 24]. Irinotecan is clearly
an example of personalized medicine in oncology. This is an area that
continues to grow as the understanding of the mechanisms of action
of anti cancer agents, and the significance of genetic mutations in
drug metabolism/exposure becomes more established.
UGT1A1*28
References
1. Toffoli, G., Cecchin, E., Coron, G., Russo, A., Buonadonna, A., D'Andrea,
M., Pasetto, L.M., Pessa, S., Errante, D., De Pangher, V., Giusto, M., Medici,
M., Gaion, F., Sandri, P, Galligioni, E., Bonura, S., Boccalon, M., Biaon,
P., Frustaci, S. (2006). The role of UGT1A1*28 polymorphism in the
Pharmacodynamics and pharmacokinetics of irinotecan in patients
with metastatic colorectal cancer,
24(19): 3061-3068.
2. Pangilinan, J.M., Khan, G.N., Zalupski, M.M. (2008). Irinotecan
pharmacogenetics:
J. Clin. Oncol.
an
overview for the
community
oncologist,
Commun. Oncol.
5(2): 99-114.
3. Shimoyama, S. (2010). Pharmacogenetics of irinotecan: an ethnicity-
based prediction of irinotecan adverse events,
World J. Gastrointest.
2(1): 14-21.
4. Nagar, S., Blanchard, R.L. (2006). Pharmacogenetics of uridine
diphosphoglucuronosyltransferase *UGT) 1A family members and its
role in patient response to irinotecan,
Surg.
38: 393-409.
5. Iyer, L, Das, S., Janisch, L., Wen, M., Ramirez, J., Karrison, T., Gleming,
G.F., Vokes, E.E., Schilsky, R.L., Ratain, M.J. (2002). UGT1A1*28
polymorphism as a determinant of irinotean disposition and toxicity,
Pharmacogenomics J.
Drug Metab. Rev.
2: 43-47.
6. Smith, N.F., Figg, W.D., Sparreboom, A. (2006). Pharmacogenetics of
irinotecan metabolism and transport: an update,
Toxicol. in Vitro
20:
163-167.
