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J Urol. 2014 Jun;191(6):1697-702. doi: 10.1016/j.juro.2013.12.011. Epub 2013 Dec 14.

DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer.

Author information

1
Hadassah Ein-Kerem Medical Center, Jerusalem, Israel. Electronic address: ogofrit@gmail.com.
2
Edith Wolfson Medical Center, Sackler Faculty of Medicine, Holon, Israel.
3
Bnai-Zion Medical Center, Haifa, Israel.
4
Meir Medical Center, Kfar Saba, Israel.
5
Sheba Medical Center, Tel Hashomer, Israel.
6
University of Arizona, Phoenix, Arizona.
7
Hillel Yafe Medical Center, Hadera, Israel.
8
Hadassah Ein-Kerem Medical Center, Jerusalem, Israel.
9
BioCancell Ltd., Jerusalem, Israel.
10
Hebrew University, Jerusalem, Israel.

Abstract

PURPOSE:

H19 is a paternally imprinted oncofetal gene expressed in various embryonic tissues and in 85% of bladder tumors but suppressed in the adult healthy bladder. BC-819 is a DNA plasmid that carries the gene for diphtheria toxin-A under regulation of the H19 promoter sequence. We assessed the efficacy and toxicity of intravesical BC-819 instillations to prevent tumor recurrence and ablate a marker lesion in a phase 2b trial.

MATERIALS AND METHODS:

A total of 47 patients with recurrent, multiple nonmuscle invasive bladder tumors in whom prior intravesical therapy had failed underwent transurethral resection of all except 1 marker tumor. Patients expressing H19 received a 6-week induction course of intravesical BC-819. Patients who achieved a complete response (absent new tumors at 3 months) were given 3 maintenance courses of 3-weekly instillations every 3 months.

RESULTS:

All patients were evaluable for adverse effects and 39 were evaluable for efficacy. Complete tumor ablation was achieved in 33% of patients and in 64% there were no new tumors at 3 months. Median time to recurrence was 11.3 months in all cases but significantly longer (22.1 months) when analyzed by response status at 3 months. Adverse events were mild. The study was limited by the small number of patients.

CONCLUSIONS:

BC-819 prevented new tumor growth in two-thirds of the patients and ablated a third of the marker lesions. Prolonged time to recurrence was observed in responding patients. These results along with the good safety profile make BC-819 a potential medication for bladder cancer.

KEYWORDS:

carcinoma; diphtheria toxin; plasmids; urinary bladder; urothelium

PMID:
24342146
DOI:
10.1016/j.juro.2013.12.011
[Indexed for MEDLINE]

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