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Pathogenetic Aspects of Metronomic Administration of Compounds with an Alleged Antitumour Effect (Review). P. 341–350

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Section: Review articles

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UDC

615.28:616-092

DOI

10.37482/2687-1491-Z151

Authors

Margarita S. Alkhuseyn-Kulyaginova* ORCID: https://orcid.org/0000-0001-5123-5289
Elizaveta M. Kotieva* ORCID: https://orcid.org/0000-0002-5595-8799
Violetta M. Kotieva* ORCID: https://orcid.org/0000-0003-1783-1073
Mohamad S. Abou Alou* ORCID: https://orcid.org/0000-0001-5573-1183
Margarita A. Dodokhova* ORCID: https://orcid.org/0000-0003-3104-827X
Inga M. Kotieva* ORCID: https://orcid.org/0000-0002-2796-9466
*Rostov State Medical University (Rostov-on-Don, Russian Federation)
Corresponding author: Margarita Dodokhova, address: per. Nakhichevanskiy 29, Rostov-on-Don, 344022, Russian Federation; e-mail: dodohova@mail.ru

Abstract

Chemotherapy is the main treatment method for malignant neoplasms. Classical administration regimens for chemotherapeutic agents are accompanied by strong side effects. Thus, there is a need for a rational mode of administration that can increase the effectiveness of chemotherapy and reduce its side effects. Development of new antitumour drugs must involve testing their pharmacological activity at various administration regimens. At the stage of preclinical studies of new compounds with an alleged antitumour effect, determining an optimal dosage regimen is an urgent task for interdisciplinary research. This article analyses literature on the possible use and effectiveness of metronomic administration of antitumour drugs in clinical practice and in preclinical studies depending on the pathogenetic mechanism of their action. According to recent research, metronomic administration of antitumour and antimetastatic drugs is, undoubtedly, a rational way to solve the problem of severe side effects and poor drug tolerability in cancer patients. The greatest antitumour effectiveness in the metronomic regimen is achieved at combined administration of compounds with different mechanisms of action. In preclinical studies of new antitumour agents, it is important to adhere to the basic principles of developing a metronomic administration regimen: 1) at the testing stage, it is advisable to perform screening administration of low doses of new compounds along with a therapy with a known antitumour drug; 2) the minimum dose of the new compound can be calculated using its maximum tolerated dose (initial approximate series of administration in the amount of 1/10 of the maximum tolerated dose).

Keywords

metronomic regimen, anticancer chemotherapy, anticancer drugs, preclinical studies, mechanism of action

References

1. Kaprin A.D., Starinskiy V.V., Shakhzadova A.O. (eds.). Sostoyanie onkologicheskoy pomoshchi naseleniyu Rossii v 2021 godu [The State of Cancer Care for the Population of Russia in 2021]. Moscow, 2022. 239 p.
2. Chubenko V.A., Zagorskaya L.A., Chubenko V.S., Moiseenko F.V., Abduioeva N.H., Zhabina A.S., Kramchaninov M.M., Shelekhova K.V., Meldo A.A., Zykov E.M., Kudryavtsev A.A., Napol’skaya E.V., Moiseenko V.M. Metronomnaya terapiya: mesto v lechenii zlokachestvennykh opukholey [ Metronomic Chemotherapy: Efficacy in Real Clinical Practice]. Prakticheskaya onkologiya, 2019, vol. 20, no. 4, pp. 289–298. DOI: 10.31917/2004289
3. Fedyanin M.Yu., Pokataev I.A., Tyulyandin S.A. Metronomnye rezhimy khimioterapii v onkologii [Metronomic Chemotherapy Regimens in Oncology]. Onkologicheskaya koloproktologiya, 2016, vol. 6, no. 1, pp. 27–35. DOI: 10.17650/2220-3478-2016-6-1-27-35
4. Dodokhova M.A., Alkhuseyn-Kulyaginova M.S., Safronenko A.V., Kotieva I.M., Shpakovskiy D.B., Milaeva E.R. Vliyanie tsisplatina i gibridnogo olovoorganicheskogo soedineniya v malykh dozakh na rost i
metastazirovanie epidermoidnoy kartsinomy Lewis v eksperimente [Effect of Cisplatin and Hybrid Organotin Compound in Low Doses on the Growth and Metastasis of Lewis Epidermoid Carcinoma in Experiment]. Eksperimental’naya i klinicheskaya farmakologiya, 2021, vol. 84, no. 8, pp. 32–35. DOI: 10.30906/0869-2092-2021-84-8-32-35
5. Wysocki P.J., Lubas M.T., Wysocka M.L. Metronomic Chemotherapy in Prostate Cancer. J. Clin. Med., 2022, vol. 11, no. 10. Art. no. 2853. DOI: 10.3390/jcm11102853
6. Maiti R. Metronomic Chemotherapy. J. Pharmacol. Pharmacother., 2014, vol. 5, no. 3, pp. 186–192. DOI: 10.4103/0976-500X.136098
7. Kerbel R.S. Inhibition of Tumor Angiogenesis as a Strategy to Circumvent Acquired Resistance to Anti-Cancer Therapeutic Agents. Bioessays, 1991, vol. 13, no. 1, pp. 31–36. DOI: 10.1002/bies.950130106
8. Hanahan D., Bergers G., Bergsland E. Less Is More, Regularly: Metronomic Dosing of Cytotoxic Drugs Can Target Tumor Angiogenesis in Mice. J. Clin. Invest., 2000, vol. 105, no. 8, pp. 1045–1047. DOI: 10.1172/JCI9872
9. Qiu H., Wang G.-M. A New Treatment Protocol Targeting Tumor Vasculature – Metronomic Chemotherapy Combined Radiotherapy. Ai Zheng, 2007, vol. 26, no. 12, pp. 1392–1396.
10. Khachatryan L.A., Shcherbakov А.P., Chikvina I.I., Nikolaeva D.M. New Approaches for Solving the Old Problem. Pediatr. Hematol. Oncol. Immunopathol., 2022, vol. 21, no. 1, pp. 122–135 (in Russ.).
DOI: 10.24287/1726-1708-2022-21-1-122-135
11. Norrby K. Metronomic Chemotherapy and Anti-Angiogenesis: Can Upgraded Pre-Clinical Assays Improve Clinical Trials Aimed at Controlling Tumor Growth? APMIS, 2014, vol. 122, no. 7, pp. 565–579. DOI: 10.1111/apm.12201
12. Kim J.Y., Kim Y.-M. Tumor Endothelial Cells as a Potential Target of Metronomic Chemotherapy. Arch. Pharmacal Res., 2019, vol. 42, no. 1, pp. 1–13. DOI: 10.1007/s12272-018-01102-z
13. Allegrini G., Falcone A., Fioravanti A., Barletta M.T., Orlandi P., Loupakis F., Cerri E., Masi G., Di Paolo A., Kerbel R.S., Danesi R., Del Tacca M., Bocci G. A Pharmacokinetic and Pharmacodynamic Study on
Metronomic Irinotecan in Metastatic Colorectal Cancer Patients. Br. J. Cancer, 2008, vol. 98, no. 8, pp. 1312–1319. DOI: 10.1038/sаj.bjc.6604311
14. Cazzaniga M.E., Cordani N., Capici S., Cogliati V., Riva F., Cerrito M.G. Metronomic Chemotherapy. Cancers (Basel), 2021, vol. 13, no. 9. Art. no. 2236. DOI: 10.3390/cancers13092236
15. Krajnak S., Battista M.J., Hasenburg A., Schmidt M. Metronomic Chemotherapy for Metastatic Breast Cancer. Oncol. Res. Treat., 2022, vol. 45, no. 1-2, pp. 12–17. DOI: 10.1159/000520236
16. Chen Y.-P., Liu X., Zhou Q., Yang K.-Y., Jin F., Zhu X.-D., Shi M., Hu G.-Q., Hu W.-H., Sun Y., et al. Metronomic Capecitabine as Adjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A Multicentre, Open-Label, Parallel-Group, Randomised, Controlled, Phase 3 Trial. Lancet, 2021, vol. 398, no. 10297, pp. 303–313. DOI:
10.1016/S0140-6736(21)01123-5
17. Cazzaniga M.E., Vallini I., Montagna E., Amoroso D., Berardi R., Butera A., Cagossi K., Cavanna L., Ciccarese M., Cinieri S., et al. Metronomic Chemotherapy (mCHT) in Metastatic Triple-Negative Breast Cancer (TNBC) Patients: Results of the VICTOR-6 Study. Breast Cancer Res. Treat., 2021, vol. 190, no. 3, pp. 415–424. DOI: 10.1007/s10549-
021-06375-5
18. Banys-Paluchowski M., Ruckhäberle E., Schütz F., Krawczyk N., Fehm T. Metronomic Chemotherapy for Primary Non-Metastatic Breast Cancer – a Systematic Review of the Literature. Geburtshilfe Frauenheilkd., 2017, vol. 77, no. 2, pp. 142–148. DOI: 10.1055/s-0043-100388
19. Orlandi P., Di Desidero T., Salvia G., Muscatello B., Francia G., Bocci G. Metronomic Vinorelbine Is Directly Active on Non Small Cell Lung Cancer Cells and Sensitizes the EGFRL858R/T790M Cells to Reversible EGFR Tyrosine Kinase Inhibitors. Biochem. Pharmacol., 2018, vol. 152, pp. 327–337. DOI: 10.1016/j.bcp.2018.04.011
20. El Darsa H., El Sayed R., Abdel-Rahman O. What Is the Real Value of Metronomic Chemotherapy in the Treatment of Gastrointestinal Cancer? Expert Opin. Pharmacother., 2021, vol. 22, no. 17, pp. 2297–2302. DOI: 10.1080/14656566.2021.1940953
21. Zsiros E., Lynam S., Attwood K.M., Wang C., Chilakapati S., Gomez E.C., Liu S., Akers S., Lele S., Frederick P.J., Odunsi K. Efficacy and Safety of Pembrolizumab in Combination with Bevacizumab and Oral
Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol., 2021, vol. 7, no. 1, pp. 78–85. DOI: 10.1001/jamaoncol.2020.5945
22. Bondarenko M., Le Grand M., Shaked Y., Raviv Z., Chapuisat G., Carrère C., Montero M.-P., Rossi M., Pasquier E., Carré M., André N. Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer. Cancers (Basel), 2021, vol. 13, no. 9. Art. no. 2239. DOI: 10.3390/cancers13092239
23. Peristeri D.V., Tepelenis K., Karampa A., Kapodistrias N., Goussia A.C., Pappas-Gogos G., Glantzounis G.K. Metronomic Chemotherapy with Cyclophosphamide for the Treatment of Advanced Hepatocellular Cancer: A Case Report. Ann. Med. Surg. (Lond.), 2021, vol. 72. Art. no. 103043. DOI: 10.1016/j.amsu.2021.103043
24. Su N.-W., Chen Y.-J. Metronomic Therapy in Oral Squamous Cell Carcinoma. J. Clin. Med., 2021, vol. 10, no. 13. Art. no. 2818. DOI: 10.3390/jcm10132818
25. Isono-Taniguchi R., Goto M., Takimoto Y., Ueda T., Wakimoto Y., Inoue K., Hori K., Ito K., Tsubamoto H. Metronomic Chemotherapy Using Oral Cyclophosphamide and Bevacizumab for Recurrent Cervical Cancer: A Multi- Institutional Retrospective Study. Gynecol. Oncol. Rep., 2022, vol. 42. Art. no. 101013. DOI: 10.1016/j.gore.2022.101013
26. Sharma A., Kataria B., Biswas B., Bakhshi S., Pushpam D. Oral Metronomic Chemotherapy Is a Cost Effective Alternative to Pazopanib in Advanced Soft Tissue Sarcoma. J. Oncol. Pharm. Pract., 2022, vol. 28, no. 3, pp. 560–568. DOI: 10.1177/10781552211000113
27. Noronha V., Patil V.M., Menon N.S., Joshi A., Goud S., More S., Kannan S., Pawar A., Nakti D., Yadav A., Shah S., Mahajan A., Janu A., Kumar R., Tibdewal A., Mummudi N., Agarwal J.P., Banavali S.D., Prabhash K. Oral Metronomic Chemotherapy After Definitive Chemoradiation in Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. Esophagus, 2022, vol. 19, no. 4, pp. 670–682. DOI: 10.1007/s10388-022-00923-8
28. Arrivi G., Spada F., Frassoni S., Bagnardi V., Laffi A., Rubino M., Gervaso L., Fazio N. Metronomic Chemotherapy in Patients with Advanced Neuroendocrine Tumors: A Single-Center Retrospective Analysis. J. Neuroendocrinol., 2022, vol. 34, no. 10. Art. no. e13189. DOI: 10.1111/jne.13189
29. Isacoff W.H., Cooper B., Bartlett A., McCarthy B., Yu K.H. ChemoSensitivity Assay Guided Metronomic Chemotherapy Is Safe and Effective for Treating Advanced Pancreatic Cancer. Cancers (Basel), 2022, vol. 14. Art. no. 2906. DOI: 10.3390/cancers14122906
30. Patil V., Noronha V., Dhumal S.B., Joshi A., Menon N., Bhattacharjee A., Kulkarni S., Ankathi S.K., Mahajan A., Sable N., Nawale K., Bhelekar A., Mukadam S., Chandrasekharan A., Das S., Vallathol D., D’Souza H.,
Kumar A., Agrawal A., Khaddar S., Rathnasamy N., Shenoy R., Kashyap L., Rai R.K., Abraham G., Saha S., Majumdar S., Karuvandan N., Simha V., Babu V., Elamarthi P., Rajpurohit A., Kumar K.A.P., Srikanth A., Ravind R., Banavali S., Prabhash K. Low-Cost Oral Metronomic Chemotherapy versus Intravenous Cisplatin in Patients with Recurrent, Metastatic, Inoperable Head and Neck Carcinoma: An Open-Label, Parallel-Group,
Non-Inferiority, Randomised, Phase 3 Trial. Lancet Glob. Health, 2020, vol. 8, no. 9, pp. e1213–e1222. DOI: 10.1016/S2214-109X(20)30275-8
31. Simsek C., Esin E., Yalcin S. Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience. J. Oncol., 2019, vol. 2019. Art. no. 5483791. DOI: 10.1155/2019/5483791
32. Chang A.E., Wu Q.V., Jenkins I.C., Specht J.M., Gadi V.K., Gralow J.R., Salazar L.G., Kurland B.F., Linden H.M. Phase I/II Trial of Combined Pegylated Liposomal Doxorubicin and Cyclophosphamide in Metastatic
Breast Cancer. Clin. Breast Cancer, 2018, vol. 18, no. 1, pp. e143–e149. DOI: 10.1016/j.clbc.2017.10.005
33. Zhong H., Lai Y., Zhang R., Daoud A., Feng Q., Zhou J., Shang J. Low Dose Cyclophosphamide Modulates Tumor Microenvironment by TGF-β Signaling Pathway. Int. J. Mol. Sci., 2020, vol. 21, no. 3. Art. no. 957. DOI: 10.3390/ijms21030957
34. Ledzewicz U., Schättler H. Application of Mathematical Models to Metronomic Chemotherapy: What Can Be Inferred from Minimal Parameterized Models? Cancer Lett., 2017, vol. 401, pp. 74–80.
DOI: 10.1016/j.canlet.2017.03.021



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