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Real-world experience with Temozolomide & Sativex in patients with recurrent High Grade Gliomas

ABSTRACT: Abstract Background Glioblastoma (GBM) is the most common malignant brain tumour in adults with a median survival from progression of 8 months. A recent phase 1 study of temozolomide (TMZ) and 1:1 CBD:THC (Sativex) offers evidence of efficacy in patients with recurrent GBM (NCT01812603). Methods All patients receiving TMZ & Sativex (75mg/m2 daily d1 – 21 q28; Sativex continuously) for relapsed GBM or grade 3 astrocytoma at our centre were identified. Patient, tumor and treatment characteristics were recorded, and response based on sequential MRI scans using modified RANO criteria assessed. Results 13 patients were treated over 18 months. The median age was 56; 69% were male. All had received initial chemo-radiotherapy (12 patients: 60 or 59.4Gy/30–33#; 1 patient: 45Gy/15#). 6 patients underwent reresection at recurrence. 4 patients were treated at first progression, 7 at second progression, and 2 at third or later progression. The median number of cycles of TMZ and sativex was 2. The combination treatment was tolerated well by all patients treated, with no Grade 3 or 4 toxicities, the only complaints being of discomfort in mouth after spray and ‘spaced out feeling’. Patients stopped treatment due to evidence of progressive disease on sequential MRI sign or physical deterioration. Median Overall Survival (OS) from initiation was 5.9 months (177 days); Progression Free Surival (PFS) at 3 months was 50%. Conclusion These results highlight some discrepancies in OS in comparison to the previous trial (NCT01812603), but our patients were treated at second/ third recurrence. We agree that the combination is well tolerated.

SUBMITTER: Shahabi L

PROVIDER: S-EPMC6789945 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with BRCA1/2 Mutation: A Korean Multicenter Study.

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| S-EPMC8197750 | biostudies-literature

Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: results of a phase 1 clinical trial.

Project description:BackgroundMebendazole is an anthelmintic drug introduced for human use in 1971 that extends survival in preclinical models of glioblastoma and other brain cancers.MethodsA single-center dose-escalation and safety study of mebendazole in 24 patients with newly diagnosed high-grade gliomas in combination with temozolomide was conducted. Patients received mebendazole in combination with adjuvant temozolomide after completing concurrent radiation plus temozolomide. Dose-escalation levels were 25, 50, 100, and 200 mg/kg/day of oral mebendazole. A total of 15 patients were enrolled at the highest dose studied of 200 mg/kg/day. Trough plasma levels of mebendazole were measured at 4, 8, and 16 weeks.ResultsTwenty-four patients (18 glioblastoma and 6 anaplastic glioma) were enrolled with a median age of 49.8 years. Four patients (at 200 mg/kg) developed elevated grade 3 alanine aminotransferase (ALT) and/or aspartate transaminase (AST) after 1 month, which reversed with lower dosing or discontinuation. Plasma levels of mebendazole were variable but generally increased with dose. Kaplan-Meier analysis showed a 21-month median overall survival with 41.7% of patients alive at 2 years and 25% at 3 and 4 years. Median progression-free survival (PFS) from the date of diagnosis for 17 patients taking more than 1 month of mebendazole was 13.1 months (95% confidence interval [CI]: 8.8-14.6 months) but for 7 patients who received less than 1 month of mebendazole PFS was 9.2 months (95% CI: 5.8-13.0 months).ConclusionMebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. Further studies are needed to determine mebendazole's efficacy in patients with malignant glioma.

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Project description: Not available

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Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas

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2024-08-28 | GSE255754 | GEO

A gene signature predicting prognosis of patients with lower-grade gliomas receiving temozolomide therapy.

Project description:Temozolomide (TMZ) has been used as a first-line therapy against lower-grade gliomas (LGGs) combined with other chemotherapy drugs. However, there has been no reliable index predicting TMZ response of patients with LGGs. In this study, we aim to investigate the relationship between gene expressions and the prognosis of TMZ therapy in LGGs. We integrated transcriptome and clinical data of 171 LGGs from the Chinese Glioma Genome Atlas (CGGA). Consensus LASSO Cox regression was used to identify 14 key genes related to different clinical outcomes under TMZ chemotherapy. We constructed and evaluated a risk score based on the 14 genes. Patients with LGGs of lower risk scores (low-risk group) generally had better survival than those LGGs of higher risk scores (high-risk group), which is independent of clinicopathological factors. High-risk patients showed activation of innate and humoral-type immunity. The prognostic contribution of the risk score was validated in an independent validation cohort of 65 patients. Besides, combined with three independent predictors (grade, IDH1 mutation status, and chr1p19q co-deletion status), we further developed a nomogram to predict the benefit of TMZ treatment in LGGs. Our results indicate that a transcriptome-based index can optimize the treatment strategy for patients with LGGs under TMZ therapy.

| S-EPMC10643648 | biostudies-literature

Checkpoint inhibitor failure in hypermutated and mismatch repair-mutated recurrent high-grade gliomas.

Project description:Background:Recurrent high-grade gliomas in adults remain a deadly cancer with median survival of less than 1 year. In the absence of effective agents, immunotherapy with checkpoint inhibitors has been adopted as a potentially beneficial next step for recurrences with hypermutated or mismatch repair-mutated phenotypes. The rationale for their use, however, is based on case reports and studies with other types of cancer. Methods:We reviewed 4 cases of hypermutated or mismatch repair-mutated recurrent high-grade gliomas treated with checkpoint inhibitors. Results:All cases had recurrent high-grade glioma that harbored either a hypermutated phenotype and/or a mismatch repair mutation. Treatment with checkpoint inhibitor therapy resulted in no significant response. Conclusions:In our experience, hypermutated or mismatch repair-mutated high-grade gliomas in adults do not respond to checkpoint inhibitors alone. This lack of efficacy is in agreement with underwhelming results of clinical trials examining checkpoint inhibitors in high-grade gliomas. The case reports of responders have been in pediatric patients with glioma and are likely a different subtype altogether.

| S-EPMC6899050 | biostudies-literature

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