BACKGROUND: 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.
BACKGROUND: 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 RFC1G80A 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.
Authors: Gaia Bistulfi; Barbara A Foster; Ellen Karasik; Bryan Gillard; Jeff Miecznikowski; Vineet K Dhiman; Dominic J Smiraglia Journal: Cancer Prev Res (Phila) Date: 2011-08-11
Authors: Catherine Wilson; Pamela J Maxwell; Daniel B Longley; Richard H Wilson; Patrick G Johnston; David J J Waugh Journal: PLoS One Date: 2012-05-09 Impact factor: 3.240
Authors: Gaia Bistulfi; Hayley C Affronti; Barbara A Foster; Ellen Karasik; Bryan Gillard; Carl Morrison; James Mohler; James G Phillips; Dominic J Smiraglia Journal: Oncotarget Date: 2016-03-22
Authors: Hayley C Affronti; Mark D Long; Spencer R Rosario; Bryan M Gillard; Ellen Karasik; Christoph S Boerlin; Anthony J Pellerite; Barbara A Foster; Kristopher Attwood; Roberto Pili; John H Wilton; Moray J Campbell; Dominic J Smiraglia Journal: Oncotarget Date: 2017-10-20