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

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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.

Original languageEnglish (US)
Pages (from-to)1971-1976
Number of pages6
JournalAnnals of Oncology
Issue number12
StatePublished - Dec 4 2009



  • Castrate resistant
  • Pemetrexed
  • Pharmacogenomics
  • Post-docetaxel
  • Prostate cancer
  • Second line

ASJC Scopus subject areas

  • Oncology
  • Hematology

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