title: Factors affecting valrubicin response in patients with bacillus Calmette-Guérin-refractory bladder carcinoma in situ.
abstract: OBJECTIVE
  Patients with bacillus Calmette-Guérin (BCG)-refractory carcinoma in situ (CIS) of the bladder are candidates for intravesical (IVe) valrubicin. This post-hoc analysis of data from the pivotal phase 3, prospective, open-label study of valrubicin evaluated the effects of patient characteristics and past treatments on the response to valrubicin.
  
  
  METHODS
  Enrolled patients had non-muscle-invasive CIS with or without concurrent papillary disease stage Ta and/or T1 for which papillary tumors had been resected before treatment, and had previously received ≥ 2 courses of IVe therapy (≥ 1 BCG course). Patients received a course of valrubicin, which consisted of 6 weekly IVe treatments of valrubicin (800 mg). Complete response was defined as no evidence of disease by urine cytology, cystoscopy, and biopsy at 3 and 6 months posttreatment. Patient characteristics, baseline urinary symptoms, and number and type of previous treatment courses and instillations were compared for complete versus nonresponders (including partial responders) to valrubicin.
  
  
  RESULTS
  Ninety patients enrolled; 87 patients with positive biopsy at initiation completed a valrubicin course and underwent the 3-month assessment. Five had missing data at 6 months. Of the remaining 82 patients, 18 demonstrated a complete response; 64 demonstrated partial or no response. For complete responders versus partial or nonresponders, differences in patient characteristics, baseline urinary symptoms, and number of previous courses or instillations of BCG or other types of treatment were not significant (P > 0.05). More complete responders had evidence of inflammation before or during valrubicin treatment (P = 0.005 vs nonresponders).
  
  
  CONCLUSIONS
  In these patients with BCG-refractory CIS, complete responders to valrubicin did not differ significantly from partial or nonresponders in the number of prior courses or instillations. The results suggest that therapy with valrubicin may be considered in appropriate candidates who have not responded to prior therapies. Cystectomy should be reconsidered when valrubicin treatment fails.
authors.affiliation: University of Chicago Medical Center, Chicago, IL 60637, USA. gsteinbe@surgery.bsd.uchicago.edu
authors.forename: Gary D
authors.initials: GD
authors.lastname: Steinberg
authors.forename: Norm D
authors.initials: ND
authors.lastname: Smith
authors.forename: Kevin
authors.initials: K
authors.lastname: Ryder
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Strangman
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Slater
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D017326:Clinical Trials, Phase III as Topic; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; C016163:valrubicin; D004317:Doxorubicin