title: Pemetrexed as second-line chemotherapy for castration-resistant prostate cancer after docetaxel failure: results from a phase II study.
abstract: OBJECTIVE
  Although there is no standard treatment after docetaxel failure in patients with castration-resistant prostate cancer (CRPC), second-line chemotherapy is increasingly required. Its mechanism of action and toxicity profile make pemetrexed suitable for testing in this setting.
  
  
  METHODS
  Patients with docetaxel-resistant CRPC received pemetrexed 500 mg/m(2) every 3 weeks for 6 courses. The usual premedication with vitamin supplementation and dexamethasone prophylaxis was regularly administered. The primary objective was to quantify the biochemical response rate.
  
  
  RESULTS
  The biochemical response rate was 10.5% (95% CI 1.3-33.1), with 2 patients showing a reduction in prostate specific antigen (PSA) of ≥50%. The null hypothesis that the PSA response rate would be less than 20% was therefore accepted, and patient accrual was stopped after the evaluation of the 19th patient. The 1-year overall survival rate was 61.5%, with a median survival of 14 months. A considerable proportion of the patients (36%) were withdrawn from the study because of hematologic and nonhematologic toxicity.
  
  
  CONCLUSIONS
  Our experience with pemetrexed in CRPC patients appears discouraging in terms of activity and toxicity. No further studies of this drug should be performed in CRPC patients.
authors.affiliation: Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. orazio.caffo@apss.tn.it
authors.forename: Orazio
authors.initials: O
authors.lastname: Caffo
authors.forename: Lucia
authors.initials: L
authors.lastname: Fratino
authors.forename: Roberto
authors.initials: R
authors.lastname: Barbieri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Perin
authors.forename: Thomas
authors.initials: T
authors.lastname: Martini
authors.forename: Teodoro
authors.initials: T
authors.lastname: Sava
authors.forename: Romana
authors.initials: R
authors.lastname: Segati
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vaccher
authors.forename: Franco
authors.initials: F
authors.lastname: Bernardo Bassan
authors.forename: Antonello
authors.initials: A
authors.lastname: Veccia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pappagallo
authors.forename: Enzo
authors.initials: E
authors.lastname: Galligioni
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002369:Castration; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D049670:History, 17th Century; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D000068437:Pemetrexed; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016879:Salvage Therapy / Q000379:methods*; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine; D017430:Prostate-Specific Antigen