PURPOSE: We studied the safety and preliminary efficacy (marker tumor ablation) of 5 doses of BC-819 given as 6 intravesical infusions in patients with superficial bladder cancer in whom intravesical therapy with bacillus Calmette-Guerin had failed. BC-819 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. MATERIALS AND METHODS: A total of 18 patients in 4 groups of 3 and 1 group of 6 received escalating doses of BC-819 intravesically during 7 weeks. Patients had low grade superficial bladder cancer, which expressed H19. The effect on a marker tumor was examined 12 weeks after starting treatment. The escalating doses were 2, 4, 6, 12 and 20 mg plasmid per intravesical treatment. Responders continued to receive BC-819 once monthly every month for 1 year. RESULTS: No dose limiting toxicity was observed. The most frequent adverse events were mild to moderate bladder discomfort, dysuria, micturition urgency, urinary tract infection, diarrhea, hypertension and asthenia. Intravesical administration of BC-819 resulted in complete ablation of the marker tumor without any new tumors in 4 of the 18 patients for a 22% overall complete response rate. Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. Nine patients received monthly maintenance, of whom 4 and 1 were disease-free at 35 and 49 weeks, respectively. CONCLUSIONS: Intravesical BC-819 causes tumor ablation following intravesical administration at doses that were well tolerated. It is worthy of continued clinical investigation.
PURPOSE: We studied the safety and preliminary efficacy (marker tumor ablation) of 5 doses of BC-819 given as 6 intravesical infusions in patients with superficial bladder cancer in whom intravesical therapy with bacillus Calmette-Guerin had failed. BC-819 is a DNA plasmid that contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. MATERIALS AND METHODS: A total of 18 patients in 4 groups of 3 and 1 group of 6 received escalating doses of BC-819 intravesically during 7 weeks. Patients had low grade superficial bladder cancer, which expressed H19. The effect on a marker tumor was examined 12 weeks after starting treatment. The escalating doses were 2, 4, 6, 12 and 20 mg plasmid per intravesical treatment. Responders continued to receive BC-819 once monthly every month for 1 year. RESULTS: No dose limiting toxicity was observed. The most frequent adverse events were mild to moderate bladder discomfort, dysuria, micturition urgency, urinary tract infection, diarrhea, hypertension and asthenia. Intravesical administration of BC-819 resulted in complete ablation of the marker tumor without any new tumors in 4 of the 18 patients for a 22% overall complete response rate. Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. Nine patients received monthly maintenance, of whom 4 and 1 were disease-free at 35 and 49 weeks, respectively. CONCLUSIONS: Intravesical BC-819 causes tumor ablation following intravesical administration at doses that were well tolerated. It is worthy of continued clinical investigation.
Authors: Samantha M Sarett; Thomas A Werfel; Linus Lee; Meredith A Jackson; Kameron V Kilchrist; Dana Brantley-Sieders; Craig L Duvall Journal: Proc Natl Acad Sci U S A Date: 2017-07-24 Impact factor: 11.205
Authors: Akrita Bhatnagar; Yuchuan Wang; Ronnie C Mease; Matthew Gabrielson; Polina Sysa; Il Minn; Gilbert Green; Brian Simmons; Kathleen Gabrielson; Siddik Sarkar; Paul B Fisher; Martin G Pomper Journal: Cancer Res Date: 2014-08-21 Impact factor: 12.701
Authors: Aya Mizrahi; Abraham Czerniak; Tally Levy; Smadar Amiur; Jennifer Gallula; Imad Matouk; Rasha Abu-lail; Vladimir Sorin; Tatiana Birman; Nathan de Groot; Abraham Hochberg; Patricia Ohana Journal: J Transl Med Date: 2009-08-06 Impact factor: 5.531