THE SINGULARITIES OF TEMOZOLOMIDE PHARMACOTHERAPEUTIC EFFECTS IN BRAIN TUMOR THERAPEUTIC APPLICATIONS
DOI:
https://doi.org/10.52340/jecm.2023.04.16Keywords:
Temozolomide, pharmacotherapeutic effects, brain tumor, therapeutic applicationsAbstract
Temozolomide is the most commonly used chemotherapy drug in patients with glioblastoma, although about half of those treated are resistant to temozolomide, and some patients eventually fail. Due to the limited effectiveness of existing therapies, immunotherapy in patients with glioblastoma is under intense investigation. However, early attempts at immunotherapy in glioblastoma patients as monotherapy have had disappointing results. Therefore, combinatorial treatment strategies are being explored. Temozolomide has multiple effects on the immune system that depend on the route of administration and dosing strategy and may have unpredictable consequences for immunotherapy. Temozolomide has both direct antitumor activity and immunomodulatory properties. The timing and dose of temozolomide significantly alters its effects on immune cells and the tumor microenvironment. The effect of temozolomide on response to new treatments such as immune checkpoint inhibitors is currently unknown. The effects of temozolomide dosing and timing, as well as the inhibition of immune checkpoints, are the subject of constant attention. Combination strategies involving temozolomide and immunotherapy should be carefully considered to ensure optimal results.
Downloads
References
Ramalho M.J., Andrade S., Coelho M.A.N., Loureiro J.A., Pereira M.C. Biophysical interaction of temozolomide and its active metabolite with biomembrane models: The relevance of drug-membrane interaction for glioblastoma multiforme therapy. Eur. J. Pharm. Biopharm. 2019; 136:156-163.
Stéphanou A., Ballesta A. pH as a potential therapeutic target to improve temozolomide antitumor efficacy: A mechanistic modeling study. Pharmacol. Res. Perspect. 2019; 7(1): e00454.
Pawlowska E., Szczepanska J., Szatkowska M., Blasiak J. An Interplay between senescence, apoptosis and autophagy in glioblastoma multiforme-role in pathogenesis and therapeutic perspective. Int. J. Mol. Sci. 2018; 19(3):889.
Patel M., McCully C., Godwin K., Balis F.M. Plasma and cerebrospinal fluid pharmacokinetics of intravenous temozolomide in non-human primates. J. Neurooncol. 2003; 61(3):203-207.
Ostermann S., Csajka C., Buclin T., Leyvraz S., Lejeune F., Decosterd L.A., Stupp R. Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients. Clin. Cancer Res. 2004; 10(11):3728-3736.
Liu H.L., Huang C.Y., Chen J.Y., Wang H.Y., Chen P.Y., Wei K.C. Pharmacodynamic and therapeutic investigation of focused ultrasound-induced blood-brain barrier opening for enhanced temozolomide delivery in glioma treatment. PLoS One. 2014; 9(12): e114311.
Martínez-Garcia M., Álvarez-Linera J., Carrato C., Ley L., Luque R., Maldonado X., et al. SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017). Clin. Transl. Oncol. 2018; 20(1):22-28. doi: 10.1007/s12094-017-1763-6.
Kong D.S., Lee J.I., Kim J.H., Kim S.T., Kim W.S., Suh Y.L., Dong S.M., Nam D.H. Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma. Neuro-oncol. 2020;12(3):289-296.
Stupp R., Hegi M.E., Mason W.P., van den Bent M.J., Taphoorn M.J.B., European organization for research and treatment of cancer brain tumour and radiation oncology groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-466.
Lin A.J., Campian J.L., Hui C., Rudra S., Rao Y.J., Thotala D., Hallahan D., Huang J. Impact of concurrent versus adjuvant chemotherapy on the severity and duration of lymphopenia in glioma patients treated with radiation therapy. J. Neurooncol. 2018;136(2):403-411.
Karachi A., Dastmalchi F., Mitchell D.A., Rahman M. Temozolomide for immunomodulation in the treatment of glioblastoma. Neuro-oncol. 2018;20(12):1566-1572.
Campian J.L., Ye X., Gladstone D.E., Ambady P., Nirschl T.R., Borrello I., Golightly M., King K.E., et al. Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas. J. Neurooncol. 2015;124(2):307-316.
Wick W., Steinbach J.P., Küker W.M., Dichgans J., et al. One week on/one week off: a novel active regimen of temozolomide for recurrent glioblastoma. Neurology. 2014;62(11):2113-2115.
Khan B.A., Khan S., White B., Eranki A. Severe pneumocystis jiroveci pneumonia in a patient on temozolomide therapy: A case report and review of literature. Respir. Med.Case Rep. 2017;22:179-182.
Akasaki Y., Kikuchi T., Homma S., Koido S., Ohkusa T., Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma. Cancer Immunol. Immunother. 2016;65(12):1499-1509.
Downloads
Published
How to Cite
Issue
Section
