Purpose: Cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of anticancer agents; its overexpression was associated with resistance to docetaxel, a commonly used drug for second-line treatment of NSCLC. Several functional single nucleotide polymorphisms (SNPs) have been associated with CYP1B1 expression and activity. The objective of this study was to retrospectively evaluate the correlation of CYP1B1 SNPs with the outcome of NSCLC patients treated with docetaxel in second or third line.
Methods: Associations between CYP1B1 4326C>G and 4390A>G polymorphisms with response, progression-free survival (PFS) and overall survival (OS) were estimated using Pearson χ(2) test, Kaplan-Meier curves and log-rank test; a multivariate analysis was performed using Cox proportional hazards modeling.
Results: A total of 65 advanced NSCLC patients were enrolled into the analysis. Median age was 66 years (range 46-81). Forty-nine patients were male; only five were never smokers. Performance status (PS) was 0 in 25 patients, 1 in 28 and 2 in 12. Histology was adenocarcinoma in 28 patients, squamous carcinoma in 22, other NSCLC in the remaining 15. At univariate analysis, stage and CYP1B1 4326C>G SNPs are associated with PFS, while PS and CYP1B1 4326C>G SNPs correlated with OS. In particular, patients with CYP1B1 4326-GG genotype had shorter PFS and OS than patients with other genotypes (PFS 1.80 vs. 2.70 months, p = 0.12; OS 3.63 vs. 9.83 months, p = 0.039). CYP1B1 4326C>G SNPs were also associated with response rate. Multivariate analysis confirmed the independent prognostic/predictive role of CYP1B1 4326C>G SNPs on OS (p = 0.042) with only a trend for PFS (p = 0.083).
Conclusions: CYP1B1 4326C>G polymorphism emerged as possible prognostic/predictive marker of activity and efficacy of docetaxel in NSCLC patients.