title: GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group.
abstract: A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity. As nuclear GSTP1 activity decreases irinotecan cytotoxicity, Val-allele carriers may benefit more from irinotecan chemotherapy. Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan. Progression-free survival (PFS) and toxicity were determined in 267 metastatic colorectal cancer (MCRC) patients who were treated with first-line capecitabine (CAP) plus irinotecan (CAPIRI), or CAP single agent in a prospective randomised phase III trial (CAIRO). GSTP1 genotype was determined by Pyrosequencing. Patients receiving CAP showed a PFS of 6.6 (Ile/Ile), 6.0 (Ile/Val) and 6.5 months (Val/Val); compared to 7.0 (Ile/Ile), 8.8 (Ile/Val) and 9.2 months (Val/Val) with CAPIRI. Median PFS was 2.7 months longer in Val-allele carriers treated with CAPIRI compared to CAP (P=0.005). Patients with the Ile/Ile genotype showed similar PFS with CAPIRI and CAP (7.0 compared to 6.6 months, P=0.972). Toxicity did not differ significantly among genotypes. GSTP1 codon 105 polymorphism may be predictive for the response to irinotecan-based chemotherapy in patients with MCRC, with the Val-allele being associated with a better outcome. Ile/Ile genotype patients do not appear to benefit from the addition of irinotecan to CAP.
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. d.m.kweekel@lumc.nl
authors.forename: D M
authors.initials: DM
authors.lastname: Kweekel
authors.forename: M
authors.initials: M
authors.lastname: Koopman
authors.forename: N F
authors.initials: NF
authors.lastname: Antonini
authors.forename: T
authors.initials: T
authors.lastname: Van der Straaten
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: H-J
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005472:Fluorouracil; D002166:Camptothecin
references.citation: Lancet. 2007 Jul 14;370(9582):143-152
references.pmid: 17630037
references.citation: Pharmacogenomics. 2007 Dec;8(12):1693-703
references.pmid: 18085999
references.citation: J Clin Oncol. 2008 Jun 1;26(16):2690-8
references.pmid: 18509181
references.citation: Ann Oncol. 2004 Oct;15(10):1453-9
references.pmid: 15367403
references.citation: Br J Cancer. 2006 Jan 30;94(2):281-6
references.pmid: 16317430
references.citation: Ther Drug Monit. 2008 Aug;30(4):504-10
references.pmid: 18641537
references.citation: Ann Oncol. 2006 Oct;17(10):1523-8
references.pmid: 16873425
references.citation: J Clin Oncol. 2001 Nov 1;19(21):4097-106
references.pmid: 11689577
references.citation: Br J Cancer. 2008 Jul 22;99(2):275-82
references.pmid: 18594531
references.citation: Cancer Res. 1994 Aug 15;54(16):4313-20
references.pmid: 8044778
references.citation: J Clin Pharmacol. 2004 Aug;44(8):854-60
references.pmid: 15286088
references.citation: Clin Pharmacol Ther. 2008 May;83(5):749-57
references.pmid: 17914442
references.citation: J Natl Cancer Inst. 2002 Jun 19;94(12):936-42
references.pmid: 12072547
references.citation: Lancet. 2007 Jul 14;370(9582):135-142
references.pmid: 17630036
references.citation: J Clin Oncol. 2007 Apr 1;25(10):1247-54
references.pmid: 17401013
references.citation: Clin Cancer Res. 2003 Aug 15;9(9):3246-53
references.pmid: 12960109
references.citation: J Clin Invest. 1998 Feb 15;101(4):847-54
references.pmid: 9466980
references.citation: Cancer Lett. 2006 Mar 8;234(1):90-106
references.pmid: 16343744
references.citation: Br J Clin Pharmacol. 2006 Oct;62(4):457-72
references.pmid: 16995867
references.citation: Jpn J Cancer Res. 2002 Sep;93(9):1047-56
references.pmid: 12359059
references.citation: Expert Opin Pharmacother. 2007 Jun;8(9):1197-210
references.pmid: 17563256
references.citation: BMC Cancer. 2007 Dec 19;7:228
references.pmid: 18093316
references.citation: Clin Pharmacol Ther. 2007 Jan;81(1):42-9
references.pmid: 17185998
references.citation: Carcinogenesis. 1998 Feb;19(2):275-80
references.pmid: 9498276
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: Eur J Biochem. 1994 Sep 15;224(3):893-9
references.pmid: 7925413