Hahn, N.Zon, R.Yu, M.Ademuyiwa, F.Jones, T.Dugan, W.Whalan, C.Shanmugam, R.Skaar, T.Sweeney, C.2010-06-102010-06-102009Annals of Oncology, 2009; 20(12):1971-19760923-75341569-8041http://hdl.handle.net/2440/58776Background: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. Materials and methods: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. Results: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. Conclusions: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.en© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.castrate resistant, pemetrexed, pharmacogenomics, post-docetaxel, prostate cancer, second lineJournal article002009414010.1093/annonc/mdp2440002721790000112-s2.0-7084909044936513Sweeney, C. [0000-0002-0398-6018]