title: Bacillus Calmette-Guerin versus epirubicin for primary, secondary or concurrent carcinoma in situ of the bladder: results of a European Organization for the Research and Treatment of Cancer--Genito-Urinary Group Phase III Trial (30906).
abstract: OBJECTIVE
  We compared the efficacy and side effects of intravesical instillations of bacillus Calmette-Guerin (BCG) and epirubicin in patients with carcinoma in situ (CIS) of the bladder.
  
  
  METHODS
  Patients with primary, secondary or concurrent CIS of the bladder were randomized to 81 mg BCG-Connaught (6 weekly instillations) or 50 mg epirubicin (8 weekly instillations). When a complete response (CR), defined as no Ta/T1 or CIS on biopsy and negative cytology, was obtained, patients in the 2 groups received maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36. When no complete response was observed, the original treatment was repeated, followed again by cystoscopy and biopsies plus cytology.
  
  
  RESULTS
  A total of 168 patients were randomized between March 1993 and April 1999 to receive BCG (84) or epirubicin (84), while 4 on epirubicin and 3 on BCG were ineligible. The majority (52%) had concurrent CIS. Primary and secondary CIS was found in 23% and 24% of cases, respectively. The overall CR rate was 56% for epirubicin and 65% for BCG (p = 0.21, 90% CI 21.5 to -2.9). When tumor was found following 2 instillation courses, further treatment was left to the investigator (BCG in 29 cases and epirubicin in 37). Time to bladder tumor recurrence after CR was longer in patients treated with BCG vs epirubicin (median 5.1 vs 1.4 years). CIS recurrences were more frequently observed in complete responders to epirubicin (45% vs 16%). No differences in time to progression or duration of survival were observed. Side effects were more frequently seen in patients on BCG with 26 on BCG and 8 on epirubicin stopping treatment due to side effects.
  
  
  CONCLUSIONS
  No significant difference in CR rates could be demonstrated with intravesical instillations of epirubicin or BCG. Time to recurrence was significantly longer in patients treated with BCG after having achieved a CR. More CIS recurrences were found in patients treated with epirubicin. For time to progression and survival longer followup is warranted. Side effects were more frequent in patients on BCG.
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands. deReyke@AMC.UVA.NL
authors.forename: Theo M
authors.initials: TM
authors.lastname: de Reijke
authors.forename: Karl Heinz
authors.initials: KH
authors.lastname: Kurth
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sylvester
authors.forename: Reg R
authors.initials: RR
authors.lastname: Hall
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brausi
authors.forename: Kees
authors.initials: K
authors.lastname: van de Beek
authors.forename: K E J
authors.initials: KE
authors.lastname: Landsoght
authors.forename: Paul
authors.initials: P
authors.lastname: Carpentier
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000188:drug therapy*; D018450:Disease Progression; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy*; D015996:Survival Rate; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D015251:Epirubicin