title: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium.
abstract: OBJECTIVE
  To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium.
  
  
  METHODS
  Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m2 intravenously on day 1 every 21 days, with vitamin B12, folic acid, and dexamethasone prophylaxis.
  
  
  RESULTS
  Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients).
  
  
  CONCLUSIONS
  Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.
authors.affiliation: Hoosier Oncology Group, Indianapolis, IN, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Roth
authors.forename: Fairooz F
authors.initials: FF
authors.lastname: Kabbinavar
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaughn
authors.forename: Michael
authors.initials: M
authors.lastname: Arning
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Curiel
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Nicol
authors.forename: Donald S
authors.initials: DS
authors.lastname: Kaufman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D019459:Urothelium
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine