Glutathione-S-transferase pi (GSTP1) codon 105 polymorphism is not associated with oxaliplatin efficacy or toxicity in advanced colorectal cancer patients.
OBJECTIVE
Oxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi (GSTP1). The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer (ACC) patients.


METHODS
A total of 91 ACC patients received capecitabine and oxaliplatin (CAPOX) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group. Tumour response was evaluated according to RECIST, toxicity was graded using CTC, and GSTP1 Ile105Val was determined by pyrosequencing.


RESULTS
Overall survival after CAPOX was similar for patients with the Ile/Ile (11.5 mo), Ile/Val (11.6 mo) and Val/Val (12.6 mo) genotypes (p=0.602). Likewise, there were no statistically significant differences in progression-free survival (p=0.252). Overall grades 3-4 toxicity was not related to genotype (p=0.313). There were no differences in any grade or grades 3-4 neurotoxicity amongst the patients who received > or =500 mg/m(2) of oxaliplatin (p-values of 0.376 and 0.772, respectively).


CONCLUSIONS
The results of this study indicate that the GSTP1 genotype is not predictive for progression-free survival or overall survival in ACC patients treated with CAPOX. Moreover, overall neurotoxicity and neurotoxicity in patients receiving 500 mg/m(2) of oxaliplatin was not associated with GSTP1 genotype.
Kweekel
Dina M
DM
Leiden University Medical Center, Department of Clinical Pharmacy and Toxicology (L-0-P), Albinusdreef 2, 2300 RC Leiden, The Netherlands. d.m.kweekel@lumc.nl
Gelderblom
Hans
H
Antonini
Ninja F
NF
Van der Straaten
Tahar
T
Nortier
Johan W R
JW
Punt
Cornelis J A
CJ
Guchelaar
Henk-Jan
HJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D003062:Codon; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004812:Epidemiologic Methods; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000235:genetics; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
D003062:Codon; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D051549:Glutathione S-Transferase pi; D005472:Fluorouracil