An Overview of the Recent Progress in Irinotecan Pharmacogenetics

• Slatter JG , SuP, SamsJP, SchaafLJ, WienkersLC: Bioactivation of the anticancer agent CPT-11 to SN-38 by human hepatic microsomal carboxylesterases and the in vitro assessment of potential drug interactions.Drug Metab. Dispos.25(10) , 1157–1164 (1997).
   PubMed Web of Science ®Google Scholar
• Iyer L , KingCD, WhitingtonPF et al.: Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1a1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes.J. Clin. Invest.101(4) , 847–854 (1998).
   PubMed Web of Science ®Google Scholar
• Haaz MC , RivoryL, RicheC, VernilletL, RobertJ: Metabolism of irinotecan (Cpt-11) by human hepatic microsomes: Participation of cytochrome P-450 3A and drug interactions.Cancer Res.58(3) , 468–472 (1998).
   PubMed Web of Science ®Google Scholar
• Garcia-Carbonero R , SupkoJG: Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins.Clin. Cancer Res.8(3) , 641–661 (2002).
   PubMed Web of Science ®Google Scholar
• Iyer L , HallD, DasS et al.: Phenotype–genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism.Clin. Pharmacol. Ther.65(5) , 576–582 (1999).
   PubMed Web of Science ®Google Scholar
• Gagne JF , MontminyV, BelangerP, JournaultK, GaucherG, GuillemetteC: Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (Sn-38).Mol. Pharmacol.62(3) , 608–617 (2002).
   PubMed Web of Science ®Google Scholar
• Jinno H , Tanaka-KagawaT, HaniokaN et al.: Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan (Cpt-11), by human UGT1A1 variants, g71r, p229q, and y486d.Drug Metab. Dispos.31(1) , 108–113 (2003).
   PubMed Web of Science ®Google Scholar
• Fujita K , AndoY, NagashimaF et al.: Genetic linkage of UGT1A7 and UGT1A9 polymorphisms to UGT1A1*6 is associated with reduced activity for SN-38 in Japanese patients with cancer.Cancer Chemother. Pharmacol.60(4) , 515–522 (2007).
   PubMed Web of Science ®Google Scholar
• Strassburg CP , OldhaferK, MannsMP, TukeyRH: Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: Identification of UGT1A7 and ugt1a10 transcripts in extrahepatic tissue.Mol. Pharmacol.52(2) , 212–220 (1997).
   PubMed Web of Science ®Google Scholar
• Santos A , ZanettaS, CresteilT et al.: Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans.Clin. Cancer Res.6(5) , 2012–2020 (2000).
   PubMed Web of Science ®Google Scholar
• Iyer L , RamirezJ, Shepard Dr et al.: Biliary transport of irinotecan and metabolites in normal and P-glycoprotein-deficient mice. Cancer Chemother. Pharmacol.49(4) , 336–341 (2002).
   PubMed Web of Science ®Google Scholar
• De Forni M , BugatR, ChabotGG et al.: Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients.Cancer Res.54(16) , 4347–4354 (1994).
   PubMed Web of Science ®Google Scholar
• Kehrer DF , SparreboomA, VerweijJ et al.: Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients.Clin. Cancer Res.7(5) , 1136–1141 (2001).
   PubMed Web of Science ®Google Scholar
• Gupta E , LestingiTM, MickR, RamirezJ, VokesEE, RatainMJ: Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea.Cancer Res.54(14) , 3723–3725 (1994).
   PubMed Web of Science ®Google Scholar
• Mathijssen RH , van Alphen RJ, Verweij J et al.: Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin. Cancer Res.7(8) , 2182–2194 (2001).
   PubMed Web of Science ®Google Scholar
• Ando Y , SakaH, AndoM et al.: Polymorphisms of udp-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis.Cancer Res.60(24) , 6921–6926 (2000).
   PubMed Web of Science ®Google Scholar
• Iyer L , DasS, JanischL et al.: UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity.Pharmacogenomics J.2(1) , 43–47 (2002).
   PubMedGoogle Scholar
• Innocenti F , UndeviaSD, IyerL et al.: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan.J. Clin. Oncol.22(8) , 1382–1388 (2004).
   PubMed Web of Science ®Google Scholar
• Marcuello E , AltesA, MenoyoA, Del Rio E, Gomez-Pardo M, Baiget M: UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br. J. Cancer91(4) , 678–682 (2004).
   PubMed Web of Science ®Google Scholar
• Rouits E , Boisdron-CelleM, DumontA, GuerinO, MorelA, GamelinE: Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients.Clin. Cancer Res.10(15) , 5151–5159 (2004).
   PubMed Web of Science ®Google Scholar
• Kim TW , InnocentiF: Insights, challenges, and future directions in irinogenetics.Ther. Drug Monit.29(3) , 265–270 (2007).
   PubMed Web of Science ®Google Scholar
• Judson R , StephensJC, WindemuthA: The predictive power of haplotypes in clinical response.Pharmacogenomics1(1) , 15–26 (2000).
   PubMedGoogle Scholar
• Mackenzie PI , BockKW, BurchellB et al.: Nomenclature update for the mammalian udp glycosyltransferase (UGT) gene superfamily.Pharmacogenet. Genomics15(10) , 677–685 (2005).
   PubMed Web of Science ®Google Scholar
• Tukey RH , StrassburgCP: Human UDP-glucuronosyltransferases: metabolism, expression, and disease.Annu. Rev. Pharmacol. Toxicol.40 , 581–616 (2000).
   PubMed Web of Science ®Google Scholar
• Guillemette C : Pharmacogenomics of human UDP-glucuronosyltransferase enzymes.Pharmacogenomics J.3(3) , 136–158 (2003).
   PubMed Web of Science ®Google Scholar
• Aono S , YamadaY, KeinoH et al.: Identification of defect in the genes for bilirubin udp-glucuronosyl-transferase in a patient with Crigler–Najjar syndrome type II.Biochem. Biophys. Res. Commun.197(3) , 1239–1244 (1993).
   PubMed Web of Science ®Google Scholar
• Aono S , YamadaY, KeinoH et al.: A new type of defect in the gene for bilirubin uridine 5´-diphosphate-glucuronosyltransferase in a patient with Crigler–Najjar syndrome type I.Pediatr. Res.35(6) , 629–632 (1994).
   PubMed Web of Science ®Google Scholar
• Aono S , AdachiY, UyamaE et al.: Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert‘s syndrome.Lancet345(8955) , 958–959 (1995).
   PubMed Web of Science ®Google Scholar
• Bosma PJ , ChowdhuryJR, BakkerC et al.: The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert‘s syndrome.N. Engl. J. Med.333(18) , 1171–1175 (1995).
   PubMed Web of Science ®Google Scholar
• Beutler E , GelbartT, DeminaA: Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism?Proc. Natl Acad. Sci. USA95(14) , 8170–8174 (1998).
   PubMed Web of Science ®Google Scholar
• Sugatani J , YamakawaK, YoshinariK et al.: Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia.Biochem. Biophys. Res. Commun.292(2) , 492–497 (2002).
   PubMed Web of Science ®Google Scholar
• Monaghan G , RyanM, SeddonR, HumeR, BurchellB: Genetic variation in bilirubin upd-glucuronosyltransferase gene promoter and Gilbert‘s syndrome.Lancet347(9001) , 578–581 (1996).
   PubMed Web of Science ®Google Scholar
• Innocenti F , GrimsleyC, DasS et al.: Haplotype structure of the udp-glucuronosyltransferase 1a1 promoter in different ethnic groups.Pharmacogenetics12(9) , 725–733 (2002).
   PubMedGoogle Scholar
• Kaniwa N , KuroseK, JinnoH et al.: Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686c>t (p229l) found in an African–American.Drug Metab. Dispos.33(3) , 458–465 (2005).
   PubMed Web of Science ®Google Scholar
• Innocenti F , LiuW, ChenP, DesaiAA, DasS, RatainMJ: Haplotypes of variants in the udp-glucuronosyltransferase1A9 and 1A1 genes.Pharmacogenet. Genomics15(5) , 295–301 (2005).
   PubMed Web of Science ®Google Scholar
• Sai K , SaekiM, SaitoY et al.: UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer.Clin. Pharmacol. Ther.75(6) , 501–515 (2004).
   PubMed Web of Science ®Google Scholar
• Han JY , LimHS, ShinES et al.: Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin.J. Clin. Oncol.24(15) , 2237–2244 (2006).
   PubMed Web of Science ®Google Scholar
• Ki CS , LeeKA, LeeSY et al.: Haplotype structure of the UDP-glucuronosyltransferase 1a1 (UGT1A1) gene and its relationship to serum total bilirubin concentration in a male Korean population.Clin. Chem.49(12) , 2078–2081 (2003).
   PubMed Web of Science ®Google Scholar
• Zhang A , XingQ, QinS et al.: Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations.Pharmacogenomics J.7(5) , 333–338 (2007).
   PubMed Web of Science ®Google Scholar
• Kohle C , MohrleB, MunzelPA et al.: Frequent co-occurrence of the TATA box mutation associated with Gilbert‘s syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians.Biochem. Pharmacol.65(9) , 1521–1527 (2003).
   PubMed Web of Science ®Google Scholar
• Yamanaka H , NakajimaM, KatohM et al.: A novel polymorphism in the promoter region of human UGT1A9 gene (UGT1A9*22) and its effects on the transcriptional activity.Pharmacogenetics14(5) , 329–332 (2004).
   PubMedGoogle Scholar
• Carlini LE , MeropolNJ, BeverJ et al.: UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan.Clin. Cancer Res.11(3) , 1226–1236 (2005).
   PubMed Web of Science ®Google Scholar
• Saeki M , SaitoY, JinnoH et al.: Haplotype structures of the UGT1A gene complex in a Japanese population.Pharmacogenomics J.6(1) , 63–75 (2006).
   PubMed Web of Science ®Google Scholar
• Ando Y , SakaH, AsaiG, SugiuraS, ShimokataK, KamatakiT: UGT1A1 genotypes and glucuronidation of sn-38, the active metabolite of irinotecan.Ann. Oncol.9(8) , 845–847 (1998).
   PubMed Web of Science ®Google Scholar
• Huang CS , LuoGA, HuangML, YuSC, YangSS: Variations of the bilirubin uridine-diphosphoglucuronosyl transferase 1A1 gene in healthy Taiwanese.Pharmacogenetics10(6) , 539–544 (2000).
   PubMedGoogle Scholar
• Hsieh SY , WuYH, LinDY, ChuCM, WuM, LiawYF: Correlation of mutational analysis to clinical features in Taiwanese patients with Gilbert‘s syndrome.Am. J. Gastroenterol.96(4) , 1188–1193 (2001).
   PubMed Web of Science ®Google Scholar
• Akaba K , KimuraT, SasakiA et al.: Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese.Biochem. Mol. Biol. Int.46(1) , 21–26 (1998).
   PubMedGoogle Scholar
• Araki K , FujitaK, AndoY et al.: Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer.Cancer Sci.97(11) , 1255–1259 (2006).
   PubMed Web of Science ®Google Scholar
• Maitland ML , GrimsleyC, Kuttab-BoulosH et al.: Comparative genomics analysis of human sequence variation in the UGT1A gene cluster.Pharmacogenomics J.6(1) , 52–62 (2006).
   PubMed Web of Science ®Google Scholar
• Girard H , VilleneuveL, Court Mh et al.: The novel UGT1A9 intronic i399 polymorphism appears as a predictor of 7-ethyl-10-hydroxycamptothecin glucuronidation levels in the liver. Drug Metab. Dispos.34(7) , 1220–1228 (2006).
   PubMed Web of Science ®Google Scholar
• Sanoff HK , SargentDJ, GreenEM, McleodHL, GoldbergRM: Racial differences in advanced colorectal cancer outcomes and pharmacogenetics: a subgroup analysis of a large randomized clinical trial.J. Clin. Oncol.27(25) , 4109–4115 (2009).
   PubMed Web of Science ®Google Scholar
• Minami H , SaiK, SaekiM et al.: Irinotecan pharmacokinetics/pharmacodynamics and ugt1a genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28.Pharmacogenet. Genomics17(7) , 497–504 (2007).
   PubMed Web of Science ®Google Scholar
• Lara PN Jr, Natale R, Crowley J et al.: Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG s0124. J. Clin. Oncol.27(15) , 2530–2535 (2009).
   PubMed Web of Science ®Google Scholar
• Cecchin E , InnocentiF, D‘andreaM et al.: Predictive role of the UGT1A1, UGT1A7, and UGT1A9 genetic variants and their haplotypes on the outcome of metastatic colorectal cancer patients treated with fluorouracil, leucovorin, and irinotecan.J. Clin. Oncol.27(15) , 2457–2465 (2009).
   PubMed Web of Science ®Google Scholar
• Esaki T , SatohT, UraT: A prospective PGX and PK/PD dose-finding study of irinotecan based on UGT1A1*6 and *28 genotyping (UGT0601).J. Clin. Oncol.27 , E14560 (2009).
   Web of Science ®Google Scholar
• Kim T , SymS, LeeS, RyuM et al.: A UGT1A1 genotype-directed Phase I study of irinotecan (CPT-11) combined with fixed dose of capecitabine in patients with metastatic colorectal cancer (MCRC).J. Clin. Oncol.27(Suppl.) , 15S (2009) (abstract 2554).
   Web of Science ®Google Scholar
• Hoskins JM , GoldbergRM, QuP, IbrahimJG, McleodHL: UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters.J. Natl Cancer Inst.99(17) , 1290–1295 (2007).
   PubMedGoogle Scholar
• Stewart CF , PanettaJC, O‘Shaughnessy Ma et al.: UGT1A1 promoter genotype correlates with SN-38 pharmacokinetics, but not severe toxicity in patients receiving low-dose irinotecan. J. Clin. Oncol.25(18) , 2594–2600 (2007).
   PubMed Web of Science ®Google Scholar
• Hosokawa M : Structure and catalytic properties of carboxylesterase isozymes involved in metabolic activation of prodrugs.Molecules13(2) , 412–431 (2008).
   PubMed Web of Science ®Google Scholar
• Satoh T , TaylorP, BosronWF, SanghaniSP, HosokawaM, La Du BN: Current progress on esterases: from molecular structure to function. Drug Metab. Dispos.30(5) , 488–493 (2002).
   PubMed Web of Science ®Google Scholar
• Xie M , YangD, LiuL, XueB, YanB: Human and rodent carboxylesterases: immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, and tumor-related expression.Drug Metab. Dispos.30(5) , 541–547 (2002).
   PubMed Web of Science ®Google Scholar
• Humerickhouse R , LohrbachK, LiL, BosronWF, DolanME: Characterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms HCE-1 and HCE-2.Cancer Res.60(5) , 1189–1192 (2000).
   PubMed Web of Science ®Google Scholar
• Xu G , ZhangW, MaMK, McLeodHL: Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan.Clin. Cancer Res.8(8) , 2605–2611 (2002).
   PubMed Web of Science ®Google Scholar
• Fukami T , NakajimaM, MaruichiT et al.: Structure and characterization of human carboxylesterase 1A1, 1A2, and 1A3 genes.Pharmacogenet. Genomics18(10) , 911–920 (2008).
   PubMed Web of Science ®Google Scholar
• Marsh S , XiaoM, YuJ et al.: Pharmacogenomic assessment of carboxylesterases 1 and 2.Genomics84(4) , 661–668 (2004).
   PubMed Web of Science ®Google Scholar
• Tanimoto K , KaneyasuM, ShimokuniT, HiyamaK, NishiyamaM: Human carboxylesterase 1A2 expressed from carboxylesterase 1A1 and 1A2 genes is a potent predictor of CPT-11 cytotoxicity in vitro.Pharmacogenet. Genomics17(1) , 1–10 (2007).
   PubMed Web of Science ®Google Scholar
• Kim SR , SaiK, Tanaka-KagawaT et al.: Haplotypes and a novel defective allele of CES2 found in a Japanese population.Drug Metab. Dispos.35(10) , 1865–1872 (2007).
   PubMed Web of Science ®Google Scholar
• Kubo T , KimSR, SaiK et al.: Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (hce-2).Drug Metab. Dispos.33(10) , 1482–1487 (2005).
   PubMed Web of Science ®Google Scholar
• Kehrer DF , MathijssenRH, VerweijJ, De Bruijn P, Sparreboom A: Modulation of irinotecan metabolism by ketoconazole. J. Clin. Oncol.20(14) , 3122–3129 (2002).
   PubMed Web of Science ®Google Scholar
• Mathijssen RH , De Jong FA, van Schaik Rh et al.: Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J. Natl Cancer Inst.96(21) , 1585–1592 (2004).
   PubMedGoogle Scholar
• Mathijssen RH , MarshS, Karlsson Mo et al.: Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin. Cancer Res.9(9) , 3246–3253 (2003).
   PubMed Web of Science ®Google Scholar
• Fukushima-Uesaka H , SaitoY, WatanabeH et al.: Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population.Hum. Mutat.23(1) , 100 (2004).
   PubMedGoogle Scholar
• Sai K , SaitoY, Fukushima-UesakaH et al.: Impact of CYP3A4 haplotypes on irinotecan pharmacokinetics in Japanese cancer patients.Cancer Chemother. Pharmacol.62(3) , 529–537 (2008).
   PubMed Web of Science ®Google Scholar
• Murayama N , NakamuraT, SaekiM et al.: CYP3A4 gene polymorphisms influence testosterone 6β-hydroxylation.Drug Metab. Pharmacokinet.17(2) , 150–156 (2002).
   PubMedGoogle Scholar
• Nakajima M , FukamiT, YamanakaH et al.: Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations.Clin. Pharmacol. Ther.80(3) , 282–297 (2006).
   PubMed Web of Science ®Google Scholar
• Sai K , KaniwaN, ItodaM et al.: Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan.Pharmacogenetics13(12) , 741–757 (2003).
   PubMedGoogle Scholar
• Chu XY , KatoY, NiinumaK, SudoKI, HakusuiH, SugiyamaY: Multispecific organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats.J. Pharmacol. Exp. Ther.281(1) , 304–314 (1997).
   PubMed Web of Science ®Google Scholar
• Chu XY , KatoY, SugiyamaY: Multiplicity of biliary excretion mechanisms for irinotecan, CPT-11, and its metabolites in rats.Cancer Res.57(10) , 1934–1938 (1997).
   PubMed Web of Science ®Google Scholar
• Nozawa T , MinamiH, SugiuraS, TsujiA, TamaiI: Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms.Drug Metab. Dispos.33(3) , 434–439 (2005).
   PubMed Web of Science ®Google Scholar
• Xiang X , JadaSR, LiHH et al.: Pharmacogenetics of SLCO1B1 gene and the impact of *1B and *15 haplotypes on irinotecan disposition in Asian cancer patients.Pharmacogenet. Genomics16(9) , 683–691 (2006).
   PubMed Web of Science ®Google Scholar
• Takane H , MiyataM, BuriokaN et al.: Severe toxicities after irinotecan-based chemotherapy in a patient with lung cancer: a homozygote for the SLCO1B1*15 allele.Ther. Drug Monit.29(5) , 666–668 (2007).
   PubMed Web of Science ®Google Scholar
• Han JY , LimHS, Shin Es et al.: Influence of the organic anion-transporting polypeptide 1b1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical outcome of patients with advanced non-small cell lung cancer. Lung Cancer59(1) , 69–75 (2008).
   PubMed Web of Science ®Google Scholar
• Takane H , KawamotoK, SasakiT et al.: Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy.Cancer Chemother. Pharmacol.63(6) , 1165–1169 (2009).
   PubMed Web of Science ®Google Scholar
• Innocenti F , KroetzDL, SchuetzE et al.: Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.J. Clin. Oncol.27(16) , 2604–2614 (2009).
   PubMed Web of Science ®Google Scholar
• Noda K , NishiwakiY, KawaharaM et al.: Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.N. Engl. J. Med.346(2) , 85–91 (2002).
   PubMed Web of Science ®Google Scholar
• Funke S , BrennerH, Chang-ClaudeJ: Pharmacogenetics in colorectal cancer: a systematic review.Pharmacogenomics9(8) , 1079–1099 (2008).
   PubMed Web of Science ®Google Scholar
• Yamamoto N , TakahashiT, KunikaneH et al.: Phase I/II pharmacokinetic and pharmacogenomic study of UGT1A1 polymorphism in elderly patients with advanced non-small cell lung cancer treated with irinotecan.Clin. Pharmacol. Ther.85(2) , 149–154 (2009).
   PubMed Web of Science ®Google Scholar
• Toffoli G , CecchinE, GaspariniG et al.: Genotype-driven Phase I study of irinotecan administered in combination with fluorouracil/leucovorin in patients with metastatic colorectal cancer.J. Clin. Oncol.28(5) , 866–871 (2009).
   PubMed Web of Science ®Google Scholar
• Toffoli G , CecchinE, CoronaG et al.: The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer.J. Clin. Oncol.24(19) , 3061–3068 (2006).
   PubMed Web of Science ®Google Scholar
• Rouits E , CharassonV, PetainA et al.: Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients.Br. J. Cancer99(8) , 1239–1245 (2008).
   PubMed Web of Science ®Google Scholar
• Cote JF , KirzinS, KramarA et al.: UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan.Clin. Cancer Res.13(11) , 3269–3275 (2007).
   PubMed Web of Science ®Google Scholar
• Mcleod HL , ParodiL, SargentDJ, MarshS et al.: UGT1A1*28, toxicity and outcome in advanced colorectal cancer: results from trial N9741.J. Clin. Oncol.24(18S) , 3520 (2006).
   Web of Science ®Google Scholar
• Massacesi C , TerrazzinoS, MarcucciF et al.: Uridine diphosphate glucuronosyl transferase 1a1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy.Cancer106(5) , 1007–1016 (2006).
   PubMed Web of Science ®Google Scholar
• Chiara S , SerraM, MarroniP, LastraioliS, PonzanelliA, TomaselloL: UGT1A1 promoter genotype and toxicity in patients with advanced colorectal cancer treated with irinotecan-containing chemotherapy.J. Clin. Oncol.23(16S) , 2016 (2005).
   Google Scholar
• Pillot GA , ReadWL, Hennenfent Kl et al.: A Phase II study of irinotecan and carboplatin in advanced non-small cell lung cancer with pharmacogenomic analysis: final report. J. Thorac. Oncol.1(9) , 972–978 (2006).
   PubMed Web of Science ®Google Scholar
• Rhodes KE , ZhangW, YangD et al.: ABCB1, SLCO1B1 and UGT1A1 gene polymorphisms are associated with toxicity in metastatic colorectal cancer patients treated with first-line irinotecan.Drug Metab. Lett.1(1) , 23–30 (2007).
   PubMedGoogle Scholar

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• UGT1A1 Allele Nomencature www.pharmacogenomics.pha.ulaval.ca/webdav/site/pharmacogenomics/shared/Nomenclature/UGT1A/UGT1A1.htm
   Google Scholar