Annals of Oncology Advance Access published online on July 15, 2009
Annals of Oncology, doi:10.1093/annonc/mdp244
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A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67
1 Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
2 Northern Indiana Cancer Research Consortium, South Bend, IN
3 Division of Biostatistics, Indiana University School of Medicine, Indianapolis, IN
4 Arnett Cancer Care, Lafayette, IN
5 Methodist Community Group Oncology Program, Indianapolis, IN
6 Fort Wayne Oncology and Hematology, Inc., Fort Wayne, IN, USA
7 Department of Medical Oncology, University of Adelaide, Adelaide, Australia
* Correspondence to: Dr C. J. Sweeney, Department of Medical Oncology, Royal Adelaide Hospital, Cancer Services, Level 4, East Wing, North Terrace, Adelaide, 5000, South Australia, Australia. Tel: +61-8-8222-2104; Fax: +61-8-8222-4358; E-mail: chris.sweeney{at}health.sa.gov.au
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.
castrate resistant, pemetrexed, pharmacogenomics, post-docetaxel, prostate cancer, second line
Received for publication January 19, 2009. Revision received March 24, 2009. Accepted for publication March 25, 2009.