ArticleNeuro-oncology2017
Timed sequential therapy of the selective T-type calcium channel blocker mibefradil and temozolomide in patients with recurrent high-grade gliomas.
Article in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01480050 (A Phase I Open Label Safety Study to Evaluate the Pharmacokinetic Profile and Tolerance of Mibefradil Dose Finding in Subjects With Recurrent High-Grade Glioma Undergoing Standard, Repeated Temozolomide Treatment), which is not on this map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Open Label Safety Study to Evaluate the Pharmacokinetic Profile and Tolerance of Mibefradil Dose Finding in Subjects With Recurrent High-Grade Glioma Undergoing Standard, Repeated Temozolomide Treatment
Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- Targeting Ion Channels for Cancer Therapy: From Pathophysiological Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- T-type calcium channels regulate medulloblastoma and can be targeted for therapy.Journal of neuro-oncology · 2025Article
- Calcium channels as pharmacological targets for cancer therapy.Clinical and experimental medicine · 2025Review
- Blockade of CaBritish journal of pharmacology · 2024Article
- The L-type calcium channel CaV1.3: A potential target for cancer therapy.Journal of cellular and molecular medicine · 2024Review
- The Gap Junction Inhibitor Octanol Decreases Proliferation and Increases Glial Differentiation of Postnatal Neural Progenitor Cells.International journal of molecular sciences · 2024Article
- Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives.Cancers · 2024Review
- Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.Cell death & disease · 2024Article
- Calcium channels as therapeutic targets in head and neck squamous cell carcinoma: current evidence and clinical trials.Frontiers in oncology · 2024Review
- Dysregulation of calcium homeostasis in cancer and its role in chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Calcium signalling pathways in prostate cancer initiation and progression.Nature reviews. Urology · 2023Review
- Review
- T-Type Calcium Channels: A Mixed Blessing.International journal of molecular sciences · 2022Review
- T-Type Calcium Channel Inhibitors Induce Apoptosis in Medulloblastoma Cells Associated with Altered Metabolic Activity.Molecular neurobiology · 2022Article
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Glioblastoma pharmacotherapy: A multifaceted perspective of conventional and emerging treatments (Review).Experimental and therapeutic medicine · 2021Review
- Role of Calcium Homeostasis in Modulating EMT in Cancer.Biomedicines · 2021Review
- Article
- A new class of radiosensitizers for glioblastoma.Oncotarget · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 12 institutions in 1 country.
Funding
Abstract
Background: Mibefradil (MIB), previously approved for treatment of hypertension, is a selective T-type calcium channel blocker with preclinical activity in high-grade gliomas (HGGs). To exploit its presumed mechanism of impacting cell cycle activity (G1 arrest), we designed a phase I study to determine safety and the maximum tolerated dose (MTD) of MIB when given sequentially with temozolomide (TMZ) in recurrent (r)HGG. Methods: Adult patients with rHGG ≥3 months from TMZ for initial therapy received MIB in 4 daily doses (q.i.d.) for 7 days followed by standard TMZ at 150-200 mg/m2 for 5 days per 28-day cycle. MIB dose escalation followed a modified 3 + 3 design, with an extension cohort of 10 patients at MTD who underwent 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET imaging, to image proliferation before and after 7 days of MIB. Results: Twenty-seven patients were enrolled (20 World Health Organization grade IV, 7 grade III; median age 50 y; median KPS 90). The MTD of MIB was 87.5 mg p.o. q.i.d. Dose-limiting toxicities were elevation of alanine aminotransferase/aspartate aminotransferase (grade 3) and sinus bradycardia. The steady-state maximum plasma concentration of MIB at the MTD was 1693 ± 287 ng/mL (mean ± SD). 18F-FLT PET imaging showed a significant decline in standardized uptake value (SUV) signal in 2 of 10 patients after 7 days of treatment with MIB. Conclusions: MIB followed by TMZ was well tolerated in rHGG patients at the MTD. The lack of toxicity and presence of some responses in this selected patient population suggest that this regimen warrants further investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.