The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis.
To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
M M
MM
Dias
Meta-analysis Unit, Department of Biostatistics and Epidemiology, Gustave-Roussy, Villejuif, France.
J-P
JP
Pignon
Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
C S
CS
Karapetis
Department of Oncologic Medicine, Gustave-Roussy, Villejuif, France.
V
V
Boige
Section of Oncology, Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
B
B
Glimelius
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, The Netherlands.
D M
DM
Kweekel
Davis Comprehensive Cancer Center, University of California, Sacramento, CA, USA.
P N
PN
Lara
Unité Mixte de Recherche S775, Institut National de la Santé et de la Recherche Médicale, Université Paris Descartes, Paris, France.
P
P
Laurent-Puig
Laboratori Biologia Molecular del Càncer, Institut Català d'Oncologia, Fundació Institut IGTP, Badalona, Spain.
E
E
Martinez-Balibrea
Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
D
D
Páez
Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
C J A
CJ
Punt
Lung and Cancer Control Committees, Fred Hutchinson Cancer Research Center, Statistical Center: SWOG, Seattle, WA, USA.
M W
MW
Redman
Experimental and Clinical Pharmacology Unit, CRO-National Cancer Institute, Aviano, Italy.
G
G
Toffoli
Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden.
M
M
Wadelius
Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
R A
RA
McKinnon
1] School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia [2] Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
M J
MJ
Sorich
D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016019:Survival Analysis; D000099148:UGT1A1 Enzyme
D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme