Isla D et al. (2004) Single nucleotide polymorphisms and outcome in docetaxel–cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol 15: 1194–1203

An individual’s response to chemotherapy may be influenced by single nucleotide polymorphisms (SNPs) at a variety of loci. Isla and colleagues from the Spanish Lung Cancer Group have considered whether SNPs in four relevant genes (ERCC1, XPD, RRM1 and MDR1) predict survival in non-small-cell lung cancer (NSCLC) patients treated with docetaxel–cisplatin.

Using genomic DNA from 62 patients with advanced NSCLC, the investigators carried out a one-step assay, to amplify the regions containing the SNPs and to generate fluorescent signals indicating which alleles were present. They then analyzed the patients’ survival, time to progression and response to therapy according to SNP genotype.

Patients with the wild-type (C/C) genotype at ERCC1 codon 118 showed significantly better survival, and longer time to progression, than those bearing one or two copies of the T allele at this position. No statistically significant differences were shown in response to therapy. The XPD, RRM1 and MDR1 SNPs tested showed no significant association with survival, time to progression or response, although this may have been due to the small number of patients studied.

The authors suggest that the predictive value of the ERCC1 118 genotype–if validated in an ongoing, larger study–might prove valuable in the design of tailored chemotherapy trials. Survival of patients bearing the T allele might be improved using non-cisplatin combinations.