IMR Press / JMCM / Volume 1 / Issue 4 / DOI: 10.31083/j.jmcm.2018.04.407
Open Access Research article
Halofuginone: a novel oral and intravesical agent for the treatment of non-muscle invasive bladder cancer
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1 Department of Urology, Rambam Health Care Campus, Haifa, Israel, P.C: 9602, Haifa, 3109601
2 Department of Cell Biology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel, P.C: 39040, Tel-Aviv, 69978
3 Department of Pathology, Carmel Medical Center, Haifa, Israel, P.C: 34336212, Haifa, Israel
4 Department of Urology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel, P.C: 12000, Jerusalem 91120
5 Department of Urology, Bnai-Zion Medical Center, Haifa, Israel, P.C: 4940, Haifa, 3339419
onativ@gmail.com (Omri Nativ)
J. Mol. Clin. Med. 2018, 1(4), 213–217; https://doi.org/10.31083/j.jmcm.2018.04.407
Submitted: 24 November 2018 | Accepted: 25 November 2018 | Published: 20 December 2018
Abstract

Background: Non-muscle invasive form (NMIBC) is a chronic disease with a high recurrence rate and requires lifelong surveillance. Various intravesical agents were shown to reduce tumor recurrence but unfortunately, none of these agents proved to be of benefit in long-term prevention of local recurrence or disease progression. Aim of Research: Previous studies have shown that Halofuginone (HF), an antiprotozoal agent, exerts anti-neoplastic activity in various cancer models. Our aim was to evaluate the in vivo activity of oral and intravesical HF treatment in an experimental mouse model harboring NMIBC. Methods: Initially, 60 mice were divided into six treatment groups to evaluate the toxicity of this anti-parasitic agent on the bladder mucosa. The second stage included 126 mice which underwent intravesical implantation with Mouse Bladder Tumor cells (MBT-2): Group 1 (n = 30) received no treatment, group 2 (n = 32) received 6 intravesical instillations of PBS, group 3 (n = 32) received 6 doses of 250 µg oral HF, whereas group 4 (n = 32) received 6 intravesical instillations of 250 µg HF. Results: The average weight of bladders, which reflects the anti-neoplastic activity, differed significantly between the control and treated groups: 88.8 mg ± 15.58 SEM and 81.2 mg ± 13.79 SEM for untreated and PBS-treated mice, respectively, versus 38.0 mg ± 4.02 SEM and 39.6 mg ± 5.97 SEM for animals treated with oral and intravesical HF, respectively. Conclusions: HF exerted a significant anti-neoplastic activity in mice bearing NMIBC upon oral as well as intravesical administration. These results may constitute the basis for the maintenance of oral treatment with HF in patients with NMIBC.

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