5-Azathin therapeutic effect on IDH1/2 mutant glioma

About 40% of gliomas have mutations in the isocitric acid dehydrogenase gene (IDH1 or IDH2)Idh1/2 mutant glioma has a better prognosisIDH1/2 mutant gliomas typically exhibit extensive DNA hypermethylation in cpG-rich structural domains (CIMP phenotypes), which are associated with changes in gene expression and accelerated tumor cell proliferation, so it is speculated that DNA methylmetanyr (DNMT) inhibitors may have better effects in treating IDH1/2 mutant gliomas5-Azathin is a DNMT inhibitor that has been approved for treatment of high-risk bone marrow abnormal hyperplasia syndrome (MDS) and acute myeloid leukemia (AML)The results of a study of 5-Azathin in idh1/2 mutant gliomas were published online in March 2020 by Laetitia Federici of the Gustav Rousey Cancer Institute at the University of Paris-Sacrestudystudy included 12 idh mutant astrocyma patients between May 2014 and December 2016; , WHO CLASS III 4 and WHO CLASS II 2 cases; 5 cases (41.7%) are IDH1 mutationwithwith smaller protoplasmic tumors with 1p/19q total loss, including WHO III 3 cases and WHO CLASS II 2 casesAll 12 patients received 2-5 (median 3) systemic treatment5-Azathin monosacine treatment 1-27 cycles, median 6 cycles, treatment intensity 75%-100%, median 90%3 patients (25%) who were treated with bevalmono (10mg/kg, Q2W) at the same timeThe interval between surgery and 5-azcytoside treatment was 7.5-165.4 months, with a median of 63.8 monthspatients followed 1.2-33.3 months after treatment, with a median of 20.0 monthsAll 12 patients showed progress, and imaging examination showed no signs of improvementMedian progression lifetime (PFS) was 4.7 months (95% CI, 2.1-7.4 months) and median total lifetime (OS) was 25.2 months (95% CI, 4.0-30.5 months)In patients who had used bexoteneta, the median PFS was 1.0 months (95% CI, 1.0-1.3 months), and in patients who had not used bebavarmono, the median PFS was 21.7 months (95% CI, 5.0-23.7 months); Five cases (41.7%) were stable and the treatment was effective, of which 2 cases (16.7%) had a stable period of more than 18 monthsIn 1 case, the tumor reinforcement of MRI-enhanced imaging weakened for 21 months after the use of monosacine 5-azthoferosin in patients receiving temequinamine, propylene barbazine-CCNU-CCV and radiation therapy of WHO Class III astrocyma (including IDH1 mutation, no 1p/19q co-missing and p16 deficiency) after the application of monotonoid 5-azanucleosineIn addition, 1 patient who had received radiation therapy, tamoxamine and PCV treatment of WHO class III small glioblastoma (including IDH1 mutation, 1p/19q total deletion and p16 wild type) treated with single-drug 5-azacytoside treatment for 22 monthstoxic reactions, controlled toxicreactions of 5-azthoferosin in AML occurredThe most common neutrophil inhibition required drug reduction, and 9 patients (75%) had a level 3-4 neutleparticle suppression toxicity, 7 of which were then treated with ascending white blood cells with granulocytic set stimulation factor (GCSF)Patients with stage 3 or 4 hematological toxicity reduced the number of treatment days per cycle to 5 days, or 5 days later for the next cycle of 5-azastine treatmentconclusions
results generally suggest that relatively slow-growing gliomas may be more suitable for treatment with 5-azthoferosinCombined with preclinical studies, it was determined that 5-azacytosin therapy can improve the efficacy of alkylin, and showed that the combination of 5-azacycin and DNA injury agents could improve the therapeutic effect of DNMT inhibitors on IDH1/2 mutant gliomas.