title: Phase II open-label study of oral piritrexim in patients with advanced carcinoma of the urothelium who have experienced failure with standard chemotherapy.
abstract: BACKGROUND
  Piritrexim is reported to have a response rate of 38% in patients with chemotherapy-naive disease and 23% for second-line therapy after chemotherapy failure. We report the results of a multiinstitutional, open-label, 2-stage, phase II study that further evaluates oral piritrexim in patients with urothelial carcinoma and who proved nonresponsive to standard chemotherapy.
  
  
  METHODS
  Eligible patients included those with bi-dimensionally measurable disease and an Eastern Cooperative Oncology Group performance status of 0-2, transitional cell carcinoma or adenocarcinoma of the urothelium, and nonresponse to > or = 1 previous standard chemotherapy regimen. Patients received piritrexim orally at 25 mg 3 times daily (every 8 hours regularly) for 5 consecutive days each week for 3 weeks, followed by a 1-week rest period. Treatment was continued until disease progression, unacceptable toxicity, or patient refusal.
  
  
  RESULTS
  Of the 23 patients enrolled, 19 patients and 22 patients were assessable for toxicity and response, respectively. Two patients required dose reduction because of toxicity, 2 patients discontinued study because of toxicity, and 6 patients had > or = 1 serious adverse event. Except for grade 1/2 pain and fatigue, gastrointestinal toxicities were the most commonly reported events, followed by fever, delirium, and myelosuppression. No objective responses were observed, with 2 patients demonstrating stable disease after 2-4 cycles. By the statistical design of the trial, further enrollment was halted because of lack of activity.
  
  
  CONCLUSIONS
  Regardless of modest side effects, oral piritrexim in heavily pretreated patients is inactive at this dose and schedule, confirming the results of a recent cooperative group trial.
authors.affiliation: Matthews Hematology Oncology Associates, Matthews, NC, USA.
authors.forename: Lance K
authors.initials: LK
authors.lastname: Lassiter
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Tummala
authors.forename: Maha H
authors.initials: MH
authors.lastname: Hussain
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005493:Folic Acid Antagonists; D011743:Pyrimidines; C024530:piritrexim