Cytochrome 450 1B1 (CYP1B1) polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC) patients

CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test.Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome.CYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.Prostate cancer is the most common malignancy in men and the second leading cause of cancer death among males in the Western World [1]. Approximately 70 to 80% of patients with advanced prostate cancer respond to medical or surgical castration [2]. When tumours become refractory to androgen withdrawal therapy, most systemic treatments offer modest benefit in terms of overall-survival (OS) [3].Two multicenter phase III randomized clinical trials, TAX 327 and SWOG 9916, showed a survival advantage in Castration-Resistant Prostate Cancer (CRPC) patients treated with taxane-based chemotherapy [4,5]. In both trials the rates of prostate-specific-antigen (PSA) response and OS were significantly higher in the docetaxel groups compared to mitoxantrone and prednisone. In particular, PSA responses were 45% and 50%, while OS was 18.9 and 17.5