title: Oral bropirimine immunotherapy of carcinoma in situ of the bladder: results of a phase II trial.
abstract: OBJECTIVE
  Bropirimine is an orally administered immunostimulant that has been shown to have activity against carcinoma in situ (CIS) of the bladder. To further assess this potential activity, bropirimine was administered to 42 patients for bladder CIS in a Phase II trial.
  
  
  METHODS
  Patients were treated with bropirimine 3.0 g/day by mouth for 3 consecutive days each week up to 1 year. Cystoscopy with biopsies and bladder wash cytology were performed quarterly.
  
  
  RESULTS
  Twenty (61%) of 33 evaluable patients converted malignant biopsies and bladder wash cytology to negative, including 6 (50%) of 12 who failed prior bacillus Calmette-Guérin (BCG) immunotherapy, 14 (67%) of 21 who had not received prior BCG therapy, and 12 (80%) of 15 with primary CIS. Median response duration exceeds 21 months. Four of the 20 responders did have a papillary tumor recurrence at 3 to 15 months, all Stage Ta or T1. Mild toxicity (grade I or II) suggestive to interferon induction or administration occurred in one third of patients. Headache, transient hepatic enzyme elevations, skin rash, and arthralgias each occurred in 5% to 14% of the patients, with nausea or emesis in 21%. Grade 1 tachycardia/palpitations or chest pain each were noted in 5%.
  
  
  CONCLUSIONS
  Oral bropirimine can induce remission of bladder CIS with acceptable toxicity at 3.0 g/day. Bropirimine may be a valuable alternative to cystectomy for some failures of BCG therapy and may have the potential to replace BCG as front-line therapy because of its ease of administration.
authors.affiliation: Department of Urology, University of Texas Health Science Center, San Antonio 78284-7845, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Sarosdy
authors.forename: B A
authors.initials: BA
authors.lastname: Lowe
authors.forename: P F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: D L
authors.initials: DL
authors.lastname: Lamm
authors.forename: S D
authors.initials: SD
authors.lastname: Graham
authors.forename: H B
authors.initials: HB
authors.lastname: Grossman
authors.forename: W A
authors.initials: WA
authors.lastname: See
authors.forename: J O
authors.initials: JO
authors.lastname: Peabody
authors.forename: T D
authors.initials: TD
authors.lastname: Moon
authors.forename: R C
authors.initials: RC
authors.lastname: Flanigan
authors.forename: E D
authors.initials: ED
authors.lastname: Crawford
authors.forename: J
authors.initials: J
authors.lastname: Morganroth
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000628:therapy*; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D003596:Cytosine; C033560:bropirimine