Keiji Inoue1, Satoshi Anai2, Kiyohide Fujimoto2, Yoshihiko Hirao2, Hiroshi Furuse3, Fumitake Kai3, Seiichiro Ozono3, Takahiko Hara4, Hideyasu Matsuyama4, Masafumi Oyama5, Munehisa Ueno5, Hideo Fukuhara6, Mamoru Narukawa7, Taro Shuin6. 1. Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan. Electronic address: keiji@kochi-u.ac.jp. 2. Department of Urology, Nara Medical University, 840, Shijo, Kashihara, Nara 634-8522, Japan. 3. Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Higashi-ku, Handayama, Hamamatsu, Shizuoka 431-3192, Japan. 4. Department of Urology, Yamaguchi University Faculty of Medicine and Health Sciences, 1-1-1, Minamikogushi, Ube, Yamaguchi 755-8505, Japan. 5. Department of Urology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1298, Japan. 6. Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan. 7. Department of Clinical Medicine (Biostatistics & Pharmaceutical Medicine), School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato, Tokyo 108-8641, Japan.
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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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.
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Authors: Marcel A Kamp; Igor Fischer; Julia Bühner; Bernd Turowski; Jan Frederick Cornelius; Hans-Jakob Steiger; Marion Rapp; Philipp J Slotty; Michael Sabel Journal: Oncotarget Date: 2016-10-11