title: The impact of intravesical gemcitabine and 1/3 dose Bacillus Calmette-Guérin instillation therapy on the quality of life in patients with nonmuscle invasive bladder cancer: results of a prospective, randomized, phase II trial.
abstract: OBJECTIVE
  Bacillus Calmette-Guérin and intravesical chemotherapy represent viable adjuvant options for intermediate risk nonmuscle invasive bladder cancer. Although bacillus Calmette-Guérin is perceived as less tolerable than intravesical chemotherapy, to our knowledge no comparative studies have addressed quality of life issues. We compared the quality of life of patients with nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine or 1/3 dose bacillus Calmette-Guérin.
  
  
  METHODS
  Our multicenter, prospective, randomized, phase II study included 120 patients with intermediate risk nonmuscle invasive bladder cancer. Of these patients 88 remained assessable at 1-year followup. Only 1 patient was withdrawn because of adverse events. Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks (maintenance monthly for 1 year) while 59 received 1/3 dose bacillus Calmette-Guérin Connaught weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6 and 12 months). Quality of life was measured by the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0) and QLQ-BLS24 (Quality of Life Superficial Bladder Cancer-Specific 24) questionnaires. Group differences were calculated using ANOVA (ANOVA/MANOVA).
  
  
  RESULTS
  Treatment was well tolerated in both groups, although local and systemic side effects were more frequently reported in the bacillus Calmette-Guérin arm. Multivariate analyses showed no significant differences between the 2 groups in all quality of life dimensions. No significant changes over time in quality of life domains were detected for patients on bacillus Calmette-Guérin and gemcitabine except for physical functioning, which decreased significantly in both groups (p = 0.002). No significant differences were detected in terms of recurrence and progression between the 2 groups at 1-year followup.
  
  
  CONCLUSIONS
  While a higher rate of side effects, albeit mild to moderate, was detected with 1/3 dose bacillus Calmette-Guérin compared to gemcitabine, our study failed to show significant differences between the 2 drugs in terms of quality of life.
authors.affiliation: Department of Urology-1, University of Turin, A.O.U. San Giovanni Battista, Turin, Italy. paolo.gontero@unito.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.forename: Marco
authors.initials: M
authors.lastname: Oderda
authors.forename: Anja
authors.initials: A
authors.lastname: Mehnert
authors.forename: Alberto
authors.initials: A
authors.lastname: Gurioli
authors.forename: Francesco
authors.initials: F
authors.lastname: Marson
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lucca
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.forename: Marianne
authors.initials: M
authors.lastname: Schmid
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pappagallo
authors.forename: Filippo
authors.initials: F
authors.lastname: Sogni
authors.forename: Francesco
authors.initials: F
authors.lastname: Sanguedolce
authors.forename: Riccardo
authors.initials: R
authors.lastname: Schiavina
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martorana
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Felix
authors.initials: F
authors.lastname: Chun
mesh_terms: D000283:Administration, Intravesical; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D011788:Quality of Life; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D001500:BCG Vaccine; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: BCG; BCG Connaught; CIS; CTCAE; Common Terminology Criteria for Adverse Events; GEM; NMIBC; QoL; TUR; bacillus Calmette-Guérin; carcinoma in situ; gemcitabine; nonmuscle invasive bladder cancer; quality of life; risk assessment; transurethral resection; urinary bladder neoplasms