title: Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study.
abstract: BACKGROUND
  Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis.
  
  
  METHODS
  Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated.
  
  
  RESULTS
  All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 m g/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p < 0.001, respectively). Five episodes of serious adverse events developed in four patients; whereas a causal relationship with the investigational agent was ruled out in all episodes.
  
  
  CONCLUSIONS
  This investigator-initiated clinical trial confirmed the effectiveness and safety of PDD for NMIBC following oral administration of 5-ALA. Both doses of 5-ALA may be clinically applicable; however, the rate of detecting tumors only by PDD was higher in the 20 mg/kg-group suggesting that this dose would be more useful.
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan. Electronic address: keiji@kochi-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Urology, Nara Medical University, 840, Shijo, Kashihara, Nara 634-8522, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Anai
authors.affiliation: Department of Urology, Nara Medical University, 840, Shijo, Kashihara, Nara 634-8522, Japan.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Urology, Nara Medical University, 840, Shijo, Kashihara, Nara 634-8522, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Higashi-ku, Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furuse
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Higashi-ku, Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Kai
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Higashi-ku, Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Department of Urology, Yamaguchi University Faculty of Medicine and Health Sciences, 1-1-1, Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Urology, Yamaguchi University Faculty of Medicine and Health Sciences, 1-1-1, Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
authors.affiliation: Department of Urology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Oyama
authors.affiliation: Department of Urology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Clinical Medicine (Biostatistics & Pharmaceutical Medicine), School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato, Tokyo 108-8641, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Narukawa
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003558:Cystoscopy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005453:Fluorescence; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester
keywords: 5-Aminolevulinic acid; Non-muscle-invasive bladder cancer; Oral administration; Photodynamic diagnosis; Randomized clinical trial