ERCC1 genotype and phenotype in epithelial ovarian cancer identify patients likely to benefit from paclitaxel treatment in addition to platinum-based therapy.
OBJECTIVE
To investigate the effect of excision repair cross-complementation group 1 (ERCC1) on treatment response and survival of patients treated with platinum chemotherapy with or without paclitaxel.


METHODS
Tumor samples from epithelial ovarian cancer patients were evaluated for ERCC1 mRNA expression and a single nucleotide polymorphism at codon 118 (C>T). Of 178 patients treated with postoperative platinum-based chemotherapy, 75 were also given paclitaxel. For all of these patients, ERCC1 expression and genotype were analyzed for associations with treatment response and survival.


RESULTS
Among the 103 patients treated with platinum without paclitaxel, the C/C genotype, compared with C/T and T/T, was associated with greater risk of disease progression and death (hazard ratio [HR], 1.95, P = .051; HR, 2.01, P = .033, respectively); high levels of ERCC1 mRNA, compared with low levels, were associated with greater risk of disease progression (HR, 2.41; P = .014). Similarly, when the ERCC1 data were combined, patients with the C/C genotype and high ERCC1 expression had greater risk for disease progression (HR, 3.73; P = .003) compared with those with low expression and non-C/C genotype. However, for the 75 patients treated with platinum plus paclitaxel, the C/C genotype and high ERCC1 expression were not associated with poor prognosis, suggesting that paclitaxel may help to alleviate ERCC1-related platinum resistance.


CONCLUSIONS
Ovarian cancer patients with high ERCC1 expression or the C/C genotype at codon 118 may benefit from the combination of platinum and paclitaxel, while those with low ERCC1 expression or the C/T or T/T genotype may respond well to platinum without paclitaxel.
Smith
Stephanie
S
Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, New Haven, CT 06520-8034, USA.
Su
Dan
D
Rigault de la Longrais
Irene A
IA
Schwartz
Peter
P
Puopolo
Manuela
M
Rutherford
Thomas J
TJ
Mor
Gil
G
Yu
Herbert
H
Katsaros
Dionyssios
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin