The effect of the domestic antitumor compound chlonisol from the class of nitrosoalkylureas on the overall survival of laboratory rodents with intracranial tumors: a meta-analysis of preclinical studies

Original article
УДК 615.277.3.+616.831.006:303.447.3
DOI: 10.29296/2618723X-2022-02-05

Ya.G. Murazov*, PhD, Researcher, Scientific Laboratory of Cancer Chemoprophylaxis and Oncopharmacology, https://orcid.org/0000-0002-6573-3112
A.N. Stukov, Doctor of Medical Sciences, Senior Researcher, Research Department of Innovative Methods of Therapeutic Oncology, and Rehabilitation https://orcid.org/0000-0002-1741-6630
Iu.G. Zmitrichenko, Junior Researcher, Research Laboratory of Cancer Chemoprophylaxis and Oncopharmacology, https://orcid.org/0000-0002-9137-9532
G.V. Tochilnikov, PhD, Head of the Scientific Laboratory of Cancer Chemoprophylaxis and Oncopharmacology, https://orcid.org/0000-0003-4232-8170

FSBI «N.N. Petrov National Medical Research Center of Oncology» of the Ministry of Healthcare of the Russian Federation,
197758, Russia, St. Petersburg, village Pesochny, Leningradskaya str., 68

* e-mail: [email protected]

Keywords: 2-[3-(2‑chloroethyl)-3‑nitrosoureido]-1 3‑propanediol lomustine temozolomide brain tumor chemotherapy rodents
Acknowledgements

The authors received no financial support for the research, authorship, and/or publication of this article.

For citation:

Murazov Ya.G., Stukov A.N., Zmitrichenko Iu.G., Tochilnikov G.V. The effect of the domestic antitumor compound chlonisol from the class of nitrosoalkylureas on the overall survival of laboratory rodents with intracranial tumors: a meta-analysis of preclinical studies. Laboratory Animals for Science. 2022; 2. https://doi.org/10.29296/2618723X-2022-02-05

Abstract

The need for new, effective, and affordable drugs for the treatment of primary and metastatic brain tumors remains unsatisfactory. Exploratory preclinical studies of chlonisol (2-[3-(2‑chloroethyl)-3‑nitrosoureido]-1,3‑propanediol) showed promising results in the treatment of experimental intracranial tumors. The aim is to apply a meta-analytical approach to estimate the combined effect size of chlonisol on overall survival (OS) in rodents with brain tumor transplants. Data for the meta-analysis were obtained from the laboratory's internal database from reports of preclinical studies of chlonisol. Eligible studies were parallel preclinical trials in rodents (mice, rats) with intracranially transplanted tumors. Antitumor activity of chlonisol was compared with active control treatment (lomustine or temozolomide). All cytostatics were administered at the maximum tolerated dose (MTD). The duration of the studies was at least 90 days. The main outcome was OS-HR (hazard ratio). We applied the inverse variance technique for the meta-analysis of HRs. In HR analysis we adopted a random effects model. The analysis included seven trials with 132 rodents. Studies were conducted between 2016 and 2022. As a murine intracranial grafts we used Ehrlich’s carcinoma, Sarcoma 180 and the HER2‑positive mammary tumor derived from a female FVB/N HER-2/neu transgenic mouse. Glioma 35 was transplanted into rats. Compared with active control, oral or intraperitoneal administration of chlonisol at MTD of 20 mg/kg, significantly reduced the risk of death by 63% (HR=0.37; 95% CI: 0.24–0.56; P<0.00001) in animals with intracranial tumors. The direction in favor of chlonisol was stable across studies despite the use of different animals and transplants, the routes of administration of chlonisol, and control treatment. No significant heterogeneity was observed between the studies (Tau²=0.03; Chi²=6.52; df=6; P=0.33; I²=8%). Compared with lomustine and temozolomide, chlonisol treatment in MTD provides an important advantage in OS in animals with intracranial tumors. Our results may serve as a basis for further study of chlonisol as a chemotherapy agent for primary and metastatic brain tumors.

Authors contribution

Ya.G. Murazov — concept and design, acquisition and statistical analysis of data, writing the manuscript.
A.N. Stukov — data collection and systematization, editing of the manuscript.
Iu.G. Zmitrichenko — data collection and systematization.
G.V. Tochilnikov — editing of the manuscript.

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Received: 2022-04-29
Reviewed: 2022-05-17
Accepted for publication: 2022-06-02

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