Explore chapters and articles related to this topic
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In the UK, temozolomide is used in combination with radiotherapy in adults for newly diagnosed glioblastoma multiforme (also known as astrocytoma), an aggressive type of brain tumor, and subsequently for monotherapy. It is also used for second-line treatment of malignant glioma in adults, and for anaplastic astrocytoma, a type of brain tumor in the young. In 2011 it was licensed in some countries for the treatment of oligodendroglioma brain tumors, thus replacing the older and less-tolerated PCV (Procarbazine-Lomustine-Vincristine) regimen. Temozolomide has also been used experimentally for the treatment of some types of melanoma.
Tumors of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
DNA methylation patterns are increasingly recognized for their importance in gliomagenesis. Methylation of the promoter region of an enzyme called O [6]-methylguanine-DNA methyltransferase (MGMT) is of particular importance in high-grade gliomas. Alkylating chemotherapy agents such as temozolomide exert their cytotoxic effect by adding alkyl groups to DNA molecules. Alkylation at the O6 position of guanine is thought to be particularly cytotoxic. MGMT is a DNA repair enzyme that removes alkyl groups from this position. Methylation of the promoter region of the MGMT gene decreases expression of the DNA repair enzyme, leaving cells more susceptible to damage from alkylating chemotherapy. Patients whose tumors possess a silenced MGMT gene (from promoter methylation) have a better response to alkylating agent chemotherapy and improved survival compared with those with activation of the MGMT gene.
Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
Temozolomide is the preferred treatment for many patients, favored because it has oral administration with few systemic side effects. The Stupp regime is typically used.185 Methyl guanine methyl transferase (MGMT) expression is probably similar to adult patients,186,187 and MGMT methylation is associated with a favorable prognosis.188
Detailed in vitro analyses of the impact of multimodal cancer therapy with hyperthermia and radiotherapy on the immune phenotype of human glioblastoma cells
Published in International Journal of Hyperthermia, 2022
Eileen Stoll, Michael Hader, Michael Rückert, Thomas Weissmann, Sebastian Lettmaier, Florian Putz, Markus Hecht, Rainer Fietkau, Andreas Rosin, Benjamin Frey, Udo S. Gaipl
To prolong survival and kill tumor cells of this very diffuse infiltrating brain tumor, radiotherapy after surgical tumor resection is regarded as standard. It is usually administered to a total dose of 60 Gy with 2 Gy per fraction over a 6-week period, in combination with temozolomide [3,6]. Other irradiation protocols have been studied, but no beneficial outcomes for total doses higher than 60 Gy have been found [7]. Rather, the risk of radiation necrosis in combination with chemotherapy has to be considered for healthy tissue. The current standard of care for GBM patients consists of concomitant administration of temozolomide at a dose of 75 mg/m2 during RT, followed by another 6 cycles of temozolomide (150–200 mg/m2 on days 1–5 every 28 days). Nausea, thrombocytopenia, and neutropenia are considered to be the most common side effects associated with temozolomide during adjuvant therapy [3,8–10].
The role of myeloid-derived suppressor cells in lung cancer and targeted immunotherapies
Published in Expert Review of Anticancer Therapy, 2022
Fateme Sheida, Sepideh Razi, Mahsa Keshavarz-Fathi, Nima Rezaei
Temozolomide is the most common chemotherapy drug used in the treatment of patients with glioblastoma. It can cause lymphopenia, which could have various effects on the response rate of immunotherapies. A research was conducted to compare the immune-modulatory effects of metronomic dose (25 mg/kg × 10 days) of temozolomide with its standard dose (50 mg/kg × 5 days) in the murine glioma models. They demonstrated that the modulation of temozolomide dose affects the peripheral and intratumoral immune microenvironments, including T-cell response to anti-PD-1 therapy [178]. The primary results of an ongoing phase II clinical trial, assessing nivolumab and temozolomide in treating recurrent or refractory SCLC patients (NCT03728361), revealed that there was an early decrease in the number of MDSCs and an increase in T-cell proliferation and function in a patient with refractory SCLC [179].
Increasing use of immunotherapy and prolonged survival among younger patients with primary CNS lymphoma: a population-based study
Published in Acta Oncologica, 2019
Magdalena Neuhauser, Thomas Roetzer, Stefan Oberndorfer, Melitta Kitzwoegerer, Franz Payer, Julia J. Unterluggauer, Johannes Haybaeck, Günther Stockhammer, Sarah Iglseder, Patrizia Moser, Claudius Thomé, Martin Stultschnig, Franz Wuertz, Tanisa Brandner-Kokalj, Serge Weis, Dave Bandke, Josef Pichler, Markus Hutterer, Karl J. Krenosz, Alexandra Boehm, Beate Mayrbaeurl, Andrea Hager-Seifert, Hannes Kaufmann, Martina Dumser, Angelika Reiner-Concin, Selma Hoenigschnabl, Waltraud Kleindienst, Markus Hoffermann, Karin Dieckmann, Barbara Kiesel, Georg Widhalm, Christine Marosi, Ulrich Jaeger, Andreas Hainfellner, Monika Hackl, Johannes A. Hainfellner, Matthias Preusser, Adelheid Woehrer
The systematic documentation of real-life patterns across second and third lines of treatment constitutes a major strength of our approach. So far, the probably largest and most detailed analysis of salvage therapy has come from the French LOC network [30]. Therein, the authors found poor overall survival for refractory/relapsed patients with many patients not receiving active salvage therapy upon relapse, and the relatively longest survival for those treated with induction CT and ASCT [30]. While we similarly found receipt of active salvage therapy the major bottleneck, our cohort differs from the French one in several aspects. First, we found a significantly higher proportion of refractory/relapsed patients (81.0 vs. 45.5%), which is, however, in line with previous studies with similarly extended follow-up times [31,32]. Second, in the Austrian cohort consolidation consisted mostly of whole-brain RT while the use of ASCT was much less prevalent, which is most likely due to a previous diagnostic period, that is, before 2010. Thus, it will be of special interest to prospectively follow the changing use of ASCT in light of newer trial results that advocate its safety and efficiency [3,33,34]. The same will be true for newer treatment approaches including PD-1 blockade [35]. Of interest, temozolomide, which is the drug of choice for many primary brain tumors such as glioma and which is being increasingly recognized also for the treatment of PCNSL [36], was rarely used in our patient population.