title: Randomized Controlled Study of the Efficacy, Safety and Quality of Life with Low Dose bacillus Calmette-Guérin Instillation Therapy for Nonmuscle Invasive Bladder Cancer.
abstract: OBJECTIVE
  The optimal dose of intravesical bacillus Calmette-Guérin for the treatment of nonmuscle invasive bladder cancer is controversial. We investigated if induction therapy with low dose bacillus Calmette-Guérin could achieve a complete response rate similar to that of standard dose bacillus Calmette-Guérin, with less toxicity and higher quality of life.
  
  
  METHODS
  After transurethral resection, patients with unresectable multiple nonmuscle invasive bladder cancer and/or carcinoma in situ were randomized to receive standard (80 mg) or low dose (40 mg) bacillus Calmette-Guérin instillation induction therapy (weekly, 8 times). The primary end point was noninferiority of low dose bacillus Calmette-Guérin with a null hypothesis of a 15% decrease in complete response rate. Secondary end points were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and quality of life using the EORTC QLQ-C30.
  
  
  RESULTS
  In an intent to treat analysis of 166 patients the complete response rates for low dose and standard dose bacillus Calmette-Guérin were 79% (95% CI 0.70-0.88) and 85% (95% CI 0.77-0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Guérin in terms of complete response could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low dose bacillus Calmette-Guérin was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047), and significantly higher quality of life scores for global quality of life, role functioning and functional impairment.
  
  
  CONCLUSIONS
  The noninferiority of low dose bacillus Calmette-Guérin was not proven. However, low dose bacillus Calmette-Guérin was associated with lower toxicity and higher quality of life compared to standard dose bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer.
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Akira
authors: A
authors: Yokomizo
authors: Department of Urology, Chutoen General Medical Center, Kakegawa, Japan.
authors: Yusuke
authors: Y
authors: Kanimoto
authors: Department of Urology, Anjo Kosei Hospital, Anjo, Japan.
authors: Takehiko
authors: T
authors: Okamura
authors: Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Seiichiro
authors: S
authors: Ozono
authors: Department of Urology, Harasanshin Hospital, Fukuoka, Japan.
authors: Hirofumi
authors: H
authors: Koga
authors: Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.
authors: Masatsugu
authors: M
authors: Iwamura
authors: Department of Urology, Sapporo City General Hospital, Sapporo, Japan.
authors: Hiroshi
authors: H
authors: Tanaka
authors: Department of Urology, Nihon University College of Medicine, Tokyo, Japan.
authors: Satoru
authors: S
authors: Takahashi
authors: Department of Urology, Okayama Medical Center, Okayama, Japan.
authors: Tomoyasu
authors: T
authors: Tsushima
authors: Department of Urology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Hiro-Omi
authors: HO
authors: Kanayama
authors: Department of Strategic Investigation on Comprehensive Cancer Network, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors: Hideyuki
authors: H
authors: Akaza
authors: Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors: Nobuo
authors: N
authors: Shinohara
authors: Department of Urology, Suzukake Central Hospital, Hamamatsu, Japan.
authors: Soichi
authors: S
authors: Mugiya
authors: Department of Urology, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan.
authors: Koichiro
authors: K
authors: Nomata
authors: Graduate School of Science and Engineering, Chuo University, Tokyo, Japan.
authors: Tsuyoshi
authors: T
authors: Nakamura
authors: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: naito@harasanshin.or.jp.
authors: Seiji
authors: S
authors: Naito
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000283:Administration, Intravesical; D000368:Aged; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011788:Quality of Life; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: administration and dosage; mycobacterium bovis; quality of life; urinary bladder neoplasms