Preview

Research and Practical Medicine Journal

Advanced search

The effectiveness of liposomal doxorubicin hydrochloride in combination with cyclophosphan in the treatment of breast cancer in an experiment

https://doi.org/10.17709/2410-1893-2021-8-4-2

Abstract

Purpose of the study. To evaluate the antitumor efficacy of liposomal doxorubicin hydrochloride in combination with tamoxifen in the treatment of breast cancer.

Materials and methods. The study included mongrel white rats (n = 30). A model of carcinogenesis (Walker 256 tumors) was created for all animals. Then we divided these rats into 3 equal groups: 1 control group (n = 10) - animals were monitored without treatment; 2 group (n = 10) - animals received neoadjuvant therapy: liposomal doxorubicin hydrochloride + cyclophosphan; 3 group (n = 10) - animals received neoadjuvant therapy with doxorubicin hydrochloride (non-liposomal) and cyclophosphan. Animals of the second and third groups received two cycles of neoadjuvant therapy. All animals were monitored for 1.5 months. We evaluated the effectiveness of antitumor therapy by measuring the size of tumors, the dynamics of their regression, and counting the number of metastases in the lungs. The toxic effects of doxorubicin hydrochloride were assessed by blood parameters: platelet and lymphocyte levels.

Results. We recorded a significant inhibition of the growth of tumor nodes in the second group of rats on the 25th day from the start of the experiment compared with the first and third groups: 36004.7, 86112.1 and 38962.4 mm3, respectively. By the end of the 3rd week of the experiment, we also noted the formation of a tumor regression trend in the 2nd and 3rd groups of animals, which was reliably maintained until the end of the observation. At the end of the experiment, the number of metastases in the first group of animals was 3 times more, in the third group almost 1.5 times more than in the second (p < 0.05)

Conclusion. The treatment of Walker 256 tumor with liposomal doxorubicin showed better efficacy and safety in comparison with non-liposomal doxorubicin. The tumor volume becomes smaller against the background of neoadjuvant chemotherapy with liposomal doxorubicin hydrochloride compared with its non-liposomal form, while there is no pronounced decrease in platelets and lymphocytes. We also recorded a significantly lower number of lung metastases in animals of the second group compared to other groups.

About the Authors

L. A. Balykova
Ogarev Mordovia State University
Russian Federation

Larisa A. Balykova – Dr. Sci. (Med.), Corresponding Member of the Russian Academy of Sciences Dr. Sci. (Med.), Professor, Head of the Department of Pediatrics, Director of the Medical Institute, SPIN: 2024-5807, AuthorID: 141643

Saransk


Competing Interests:

Authors report no conflict of interest.



V. I. Inchina
Ogarev Mordovia State University
Russian Federation

Vera I. Inchina – Dr. Sci. (Med.), Professor, Head of the Department of Pharmacology and Clinical Pharmacology with a course in pharmaceutical technology, SPIN: 8616-6518, AuthorID: 331979

Saransk


Competing Interests:

Authors report no conflict of interest.



T. V. Tarasova
Ogarev Mordovia State University
Russian Federation

Tatiana V. Tarasova – Dr. Sci. (Biol.), Professor at the Psychology Department, SPIN: 1726-3994, AuthorID: 96588

68 Bolshevistskaya Str., Saransk 430005, Russian Federation


Competing Interests:

Authors report no conflict of interest.



L. M. Mosina
Ogarev Mordovia State University
Russian Federation

Larisa M. Mosina – Dr. Sci. (Med.), Professor of the Department of Hospital Therapy, SPIN: 2390-1111, AuthorID: 687543

Saransk


Competing Interests:

Authors report no conflict of interest.



E. N. Gvozdikova
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Evgeniya N. Gvozdikova – Cand. Sci. (Med.), Associate Professor of the Department of General and Clinical Dentistry, SPIN: 2562-4392, AuthorID: 736893

Moscow


Competing Interests:

Authors report no conflict of interest.



D. A. Khaydar
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Dalila A. Khaydar – assistant at the Department of General Dentistry, SPIN: 3830-9356, AuthorID: 1056773

Moscow


Competing Interests:

Authors report no conflict of interest.



G. I. Myandina
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Galina I. Myandina – Dr. Sci. (Biol.), Professor of the Department of Biology and General Genetics of the Medical Institute, SPIN: 2635-2234, AuthorID: 90610

Moscow


Competing Interests:

Authors report no conflict of interest.



S. M. Ryzhakin
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Sergei M. Ryzhakin – Cand. Sci. (Biol.), Associate Professor of the Department of Human Anatomy, SPIN: 3369-9541, AuthorID: 424659

Moscow


Competing Interests:

Authors report no conflict of interest.



I. V. Saushev
Ogarev Mordovia State University
Russian Federation

Igor V. Saushev – Dr. Sci. (Med.), Professor of the Department of Anesthesiology and Resuscitation with courses in Valeology, Life Safety and Disaster Medicine, SPIN: 1200-4091, AuthorID: 430327

Saransk


Competing Interests:

Authors report no conflict of interest.



References

1. Vykhristyuk YuV, Roitberg GE, Dorosh ZhV, Karaseva NV, Akobova RA. Preventive measures against development of breast cancer. South Russian Journal of Cancer. 2021;2(1):50-56. (In Russ.). https://doi.org/10.37748/2686-9039-2021-2-1-6

2. Vladimirova LYu, Storozhakova AE, Snezhko TA, Strakhova LK, Abramova NA, Kabanov SN, et al. Hormone-positive HER2-negative metastatic breast cancer: decision making in real clinical practice. South Russian Journal of Cancer. 2020;1(2):46-51. (In Russ.). https://doi.org/10.37748/2687-0533-2020-1-2-6

3. Speransky DL, Tkachenko LV, Vdovin SV, Andreeva MV, Selikhova MS, Zharkin NA. The analyses of life quality of patients with breast cancer in case of antitumoral treatment. Medical News of North Caucasus. 2015;10(4):438-440. (In Russ.). https://doi.org/10.14300/mnnc.2015.10108

4. Dzhubalieva SK, Kozlov JP, Pugachev KK, Hamann TL. Influence of ecological factors on dynamics of parameters of the hormonal status at an estimation of ways of deenergizing of function of ovaries at the patients, suffering a cancer of a mammary gland. RUDN Journal of Medicine. 2009;(2):55-60. (In Russ.).

5. Volkova MS, Astashov VV, Kazakov OV, Larionov PM, Chepik VI. Investigation of lymph nodes at experimental cancerogenesis of mammary gland. Bulletin of Novosibirsk State University. Series: Biology, Clinical Medicine. 2011;9(1):152-158. (In Russ.).

6. Liu W, Chen W, Zhang X, Zhao P, Fan Z, Bi L, et al. Higher efficacy and reduced adverse reactions in neoadjuvant chemotherapy for breast cancer by using pegylated liposomal doxorubicin compared with pirarubicin. Sci Rep. 2021 Jan 8;11(1):199. https://doi.org/10.1038/s41598-020-80415-w

7. Fraguas-Sanchez AI, Martin-Sabroso C, Fernandez-Carballido A, Torres-Suarez AI. Current status of nanomedicine in the chemotherapy of breast cancer. Cancer Chemother Pharmacol. 2019 Oct;84(4):689-706. https://doi.org/10.1007/s00280-019-03910-6

8. Si Y, Zhang Y, Ngo HG, Guan J-S, Chen K, Wang Q, et al. Targeted Liposomal Chemotherapies to Treat Triple-Negative Breast Cancer. Cancers (Basel). 2021 Jul 26;13(15):3749. https://doi.org/10.3390/cancers13153749

9. Pokataev IA, Tyulyandina AS, Chitia LV, Tyulyandin SA. Long-term effect of pegylated liposomal doxorubicin in recurrent platinum-resistant ovarian cancer: a clinical case. Tumors of female reproductive system. 2015;11(4):81-86. (In Russ.). https://doi.org/10.17650/1994-4098-2015-11-4-81-86

10. Bessmeltsev S.S. Multiple myeloma (lecture). Bulletin of Hematology. 2014;10(3):6-39. (In Russ.).

11. Furedia A, Szebenyi K, Toth S, Cserepes M, Hamori L, Nagy V, et al. Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a genetically engineered mouse model of breast cancer. J Control Release. 2017 Sep 10;261:287-296. https://doi.org/10.1016/jjconrel.2017.07.010

12. Dong M, Luo L, Ying X, Lu X, Shen J, Jiang Z, et al. Comparable efficacy and less toxicity of pegylated liposomal doxorubicin versus epirubicin for neoadjuvant chemotherapy of breast cancer: a case-control study. Onco Targets Ther. 2018;11:4247-4252. https://doi.org/10.2147/OTT.S162003

13. Zhao M, Ding X-F, Shen J-Y, Zhang X-P, Ding X-W, Xu B. Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice. J Zhejiang Univ Sci B. 2017 Jan;18(1):15-26. https://doi.org/10.1631/jzus.B1600303

14. Wenningmann N, Knapp M, Ande A, Vaidya TR, Ait-Oudhia S. Insights into Doxorubicin-induced Cardiotoxicity: Molecular Mechanisms, Preventive Strategies, and Early Monitoring. Mol Pharmacol. 2019 Aug;96(2):219-232. https://doi.org/10.1124/mol.119.115725

15. Kepinska M, Kizek R, Milnerowicz H. Fullerene as a doxorubicin nanotransporter for targeted breast cancer therapy: Capillary electrophoresis analysis. Electrophoresis. 2018 Sep;39(18):2370-2379. https://doi.org/10.1002/elps.201800148

16. Khasraw M, Bell R, Dang C. Epirubicin: is it like doxorubicin in breast cancer? A clinical review. Breast. 2012 Apr;21(2):142-149. https://doi.org/10.1016/j.breast.2011.12.012

17. Chowdhury N, Chaudhry S, Hall N, Olverson G, Zhang Q-J, Mandal T, et al. Targeted Delivery of Doxorubicin Liposomes for Her-2+ Breast Cancer Treatment. AAPS PharmSciTech. 2020 Jul 21;21(6):202. https://doi.org/10.1208/s12249-020-01743-8

18. Ghignaffi PV da C, Nogueira LJ, Lehnen AM, Leguisamo NM. Cardioprotective effects of exercise training on doxorubicin-induced cardiomyopathy: a systematic review with meta-analysis of preclinical studies. Sci Rep. 2021 Mar 18;11(1):6330. https://doi.org/10.1038/s41598-021-83877-8

19. Gkionis L, Campbell RA, Aojula H, Harris LK, Tirella A. Manufacturing drug co-loaded liposomal formulations targeting breast cancer: Influence of preparative method on liposomes characteristics and in vitro toxicity. Int J Pharm. 2020 Nov 30;590:119926. https://doi.org/10.1016/j.ijpharm.2020.119926

20. Tsai I-C, Hung C-C. Efficacy Of Pegylated Liposomal Doxorubicin-based Neoadjuvant Chemotherapy In Breast Cancer: A Single Center Experience. Clinical and Investigative Medicine. 2021 Mar 21;44(1):7-14. https://doi.org/10.25011/cim.v44i1.35196

21. Shafei A, El-Bakly W, Sobhy A, Wagdy O, Reda A, Aboelenin O, et al. A review on the efficacy and toxicity of different doxorubicin nanoparticles for targeted therapy in metastatic breast cancer. Biomed Pharmacother. 2017 Nov;95:1209-1218. https://doi.org/10.1016/j.biopha.2017.09.059

22. Franco YL, Vaidya TR, Ait-Oudhia S. Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Breast Cancer (Dove Med Press). 2018;10:131-141. https://doi.org/10.2147/BCTT.S170239

23. Szmit S, Grela-Wojewoda A, Talerczyk M, Kufel-Grabowska J, Streb J, Smok-Kalwat J, et al. Predictors of new-onset heart failure and overall survival in metastatic breast cancer patients treated with liposomal doxorubicin. Sci Rep. 2020 Oct 28;10(1):18481. https://doi.org/10.1038/s41598-020-75614-4

24. Yang FO, Hsu NC, Moi S-H, Lu Y-C, Hsieh C-M, Chang K-J, et al. Efficacy and toxicity of pegylated liposomal doxorubicin-based chemotherapy in early-stage breast cancer: a multicenter retrospective case-control study. Asia Pac J Clin Oncol. 2018 Jun;14(3):198-203. https://doi.org/10.1111/ajco.12771


Supplementary files

Review

For citations:


Balykova L.A., Inchina V.I., Tarasova T.V., Mosina L.M., Gvozdikova E.N., Khaydar D.A., Myandina G.I., Ryzhakin S.M., Saushev I.V. The effectiveness of liposomal doxorubicin hydrochloride in combination with cyclophosphan in the treatment of breast cancer in an experiment. Research and Practical Medicine Journal. 2021;8(4):23-32. (In Russ.) https://doi.org/10.17709/2410-1893-2021-8-4-2

Views: 1541


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-1893 (Online)