Ivermectin and Mebendazole as Adjunctive Therapy in High-Grade Glioma and Other Intracranial Tumors: A Retrospective Compilation of Publicly Reported Cases
Retrospective Case Series — Draft Manuscript — Not Peer-Reviewed
Manuscript compiled July 2026. This document has not been submitted to, or evaluated by, any peer-reviewed journal. It is presented in structured manuscript format for internal editorial and reference purposes only.
Abstract
Background: Glioblastoma and other high-grade intracranial tumors carry a poor prognosis despite maximal standard-of-care treatment. Ivermectin and mebendazole, both approved antiparasitic agents, have shown anticancer activity in preclinical glioma models, and a retrospective cohort (METRICS, n=95) has previously reported a survival association when mebendazole was added to a four-drug adjunctive regimen.
Methods: We compiled 38 individually described cases and one previously published retrospective cohort (n=95) from a single publicly accessible source page. Case-level data (diagnosis, prior/concurrent conventional treatment, reported regimen, follow-up duration, and reported outcome) were abstracted as stated by the original poster, without independent verification against medical records.
Results: Of the 38 individually documented cases, 37 (97%) reported a stable, partially regressed, or completely resolved outcome at last follow-up (range 2–16 months); approximately half involved concurrent or recent conventional treatment. The retrospective cohort reported a median survival increase from approximately 15 to 27 months with a four-drug regimen (mebendazole, atorvastatin, metformin, doxycycline) added to standard care.
Conclusions: This compilation cannot support conclusions about efficacy. The near-uniform rate of favorable outcomes across single-source, unverified, self-selected reports is more consistent with reporting and survivorship bias than with a treatment effect, and confounding with concurrent conventional therapy is present in a substantial fraction of cases. The one dataset with a defined denominator and protocol (METRICS) is a retrospective, non-randomized cohort. Prospective, controlled trials are required before any efficacy claim is warranted.
Keywords: glioblastoma; drug repurposing; ivermectin; mebendazole; case series; cancer stem cells; retrospective cohort
1. Introduction
Glioblastoma (GBM) remains among the most lethal solid tumors, with median overall survival of approximately 12–15 months following maximal safe resection, radiotherapy, and temozolomide chemotherapy.1 Recurrence is near-universal, driven in part by treatment-resistant cancer stem cell populations, intratumoral heterogeneity, and limited drug penetration across the blood–brain barrier.
Drug repurposing — applying agents with established safety and pharmacokinetic profiles to new indications — has been proposed as a pragmatic route to identify adjunctive glioma therapies. Ivermectin and mebendazole, both antiparasitic agents with decades of clinical use, have shown activity against glioma cell lines and stem-like populations in preclinical models, including effects on Wnt/β-catenin and PI3K/Akt signaling and on microtubule dynamics.2,3 Mebendazole has an existing institutional patent filing for glioblastoma treatment and has been evaluated in a small number of registered pediatric brain tumor trials.
Clinical evidence in humans, however, is limited almost entirely to one retrospective cohort and a body of individually reported cases shared through social media rather than through peer-reviewed case report channels. This manuscript compiles and formally tabulates that case-level material so its evidentiary weight can be assessed on its own terms, rather than as a narrative sequence of testimonials.
2. Methods
2.1 Case ascertainment. All case-level material originates from a single publicly accessible web page maintained by the corresponding editorial group (5), which in turn compiled cases predominantly from public posts (X/Twitter and Substack) by one physician, Dr. William Makis, relaying accounts provided to him by patients or family members, plus isolated posts from other individuals. This is a convenience sample of self-selected, publicly shared reports — it is not a systematic case ascertainment process, a clinic registry, or a literature search, and no attempt was made to identify or include cases with unfavorable or fatal outcomes.
2.2 Data abstraction. For each case we recorded: age/sex where stated; diagnosis and grade; prior or concurrent conventional treatment (surgery, radiotherapy, chemotherapy, or targeted therapy); the reported drug regimen and dose, as stated by the source; duration of follow-up; and the reported outcome, categorized post hoc into complete response, partial regression, stable/no progression, or no outcome reported. No independent verification of imaging, pathology, or medical records was performed or was possible from the source material.
2.3 Separate cohort data. One additional dataset, the METRICS retrospective analysis (Care Oncology Clinic, UK; n=95; NCT02201381), was identified as a previously published, independently reviewed retrospective cohort with a defined protocol and treated as methodologically distinct from the 38 individual reports.
2.4 Evidence grading. Each entry is graded using an adapted Oxford CEBM framework: Level 3–4 for the retrospective cohort with a defined denominator; Level 4/5 for individually reported, unverified cases.
3. Results
3.1 Case characteristics. Thirty-eight individual cases were identified, spanning glioblastoma (n≈16), astrocytoma/anaplastic astrocytoma (n≈5), oligodendroglioma/anaplastic oligodendroglioma (n≈5), diffuse intrinsic pontine glioma (n≈2), medulloblastoma (n≈3), ependymoma, brain sarcoma, ganglioglioma, and unspecified brain cancer (remainder). Approximately 9 of 38 cases involved pediatric patients. Reported follow-up ranged from 2 to 16 months. Approximately half of cases (19/38) reported concurrent or recent surgery, radiotherapy, and/or chemotherapy alongside the repurposed-drug regimen.
Table 1. Individually reported cases (n=38), abstracted from source material.
| Case | Age/Sex/Region | Diagnosis | Prior/Concurrent Tx | Reported Regimen | F/U | Reported Outcome | Evidence Level |
|---|---|---|---|---|---|---|---|
| 133 | 9y M, Colombia | Medulloblastoma | Chemo (6 cycles), RT (20 tx) | IVM 1mg/kg/d; MBZ 1000mg/d | 3mo | Complete response | 4/5 |
| 132 | 60F, Ohio | GBM, IDH-WT | None | IVM 1–2mg/kg/d; MBZ 1500mg/d | 16mo | Stable | 4/5 |
| 131 | 7F, Australia | Ependymoma | 2× surgery+RT | IVM 0.5mg/kg/d; MBZ 1000mg/d | 5mo | No recurrence | 4/5 |
| 130 | 55M, Canada | Anaplastic oligodendroglioma | TMZ, RT, lomustine/procarbazine/etoposide | IVM 1.5mg/kg/d; MBZ 1500mg/d; CBD 100mg/d | 14mo | No growth | 4/5 |
| 129 | 17M, Canada | DIPG | Hospice referral (prior) | IVM 1.5mg/kg/d; MBZ 2000mg/d | 3mo | Functional improvement | 4/5 |
| 128 | 30F, Canada | Brain sarcoma (CIC-r) | 3× surgery+RT (concurrent) | IVM 1.5mg/kg/d; MBZ 1500mg/d | 3mo | Complete response | 4/5 |
| 127 | 51M, Canada | GBM | Surgery+chemoradiation (aborted) | IVM 1.5mg/kg/d; MBZ 1400mg/d | 12mo | Partial regression | 4/5 |
| 126 | 47F, California | Anaplastic xanthoastrocytoma | 2× surgery; +tovorafenib later | IVM 1.5mg/kg/d; MBZ 1500–2000mg/d | 10mo | No growth | 4/5 |
| 125 | 67M, France | Oligodendroglioma Gr.2 | Declined surgery/chemo | IVM 1.0→1.6mg/kg/d; MBZ 1500→2000mg/d; niclosamide 2000mg/d | 6mo | Stable, seizures resolved | 4/5 |
| 124† | 61F, Kentucky | Oligodendroglioma Gr.2 | None | IVM+MBZ (dose NS) | 11mo | Partial regression | 4/5 |
| 123 | 9M, Colombia | Medulloblastoma | RT + vincristine (concurrent) | IVM+MBZ, escalating (dose NS) | 3mo | Complete response | 4/5 |
| 122 | 55M, Canada | Anaplastic oligodendroglioma | None; palliative referral after progression | IVM+MBZ (dose NS) | 8–9mo | Stabilized after progression | 4/5 |
| 121 | 35F, Canada | GBM (6cm) | Surgery+chemo (concurrent) | IVM+MBZ (dose NS) | 10mo | No regrowth | 4/5 |
| 120 | 71F, Colorado | GBM | None | IVM+MBZ (dose NS) | 6mo | No growth | 4/5 |
| 119 | 69F, Scotland | GBM, IDH1-WT | None | IVM 60–72mg/d w/DMSO; FBZ 1332mg/d | 6mo | Partial regression | 4/5 |
| 118 | 34M, South Carolina | GBM, IDH-WT | None | IVM 1.5mg/kg/d; MBZ 1500mg/d; CBD | 3mo | Partial regression | 4/5 |
| 117 | 24M, New Zealand | Astrocytoma Gr.3 | None | IVM 108mg/d; MBZ 1500mg/d | 10mo | No growth | 4/5 |
| 116 | 50M, Indiana | GBM | Surgery+RT+TMZ (concurrent) | IVM 0.5mg/kg/d; MBZ 1500mg/d; CBD | 10mo | No growth/recurrence | 4/5 |
| 115 | 12M, New York | Astrocytoma | Selumetinib (concurrent) | IVM+MBZ+FBZ (dose NS) | 6mo | Partial regression (40%) | 4/5 |
| 114 | 15M, Canada | High-grade glioma | Surgery(partial)+RT (concurrent) | Staged IVM/FBZ/MBZ up to IVM 48mg+MBZ 1500mg/d | 2mo | Partial regression (~65–70%) | 4/5 |
| 113 | 47M, Turkey | GBM | Surgery(98%)+chemo/RT | IVM 70mg/d; FBZ 888mg/d; MBZ 1000mg/d | 9mo | Complete response | 4/5 |
| 112 | 69M, Kentucky | GBM (4.5cm) | None | IVM 2mg/kg/d; MBZ 1500→2000mg/d; FBZ; CBD | 12mo | Sustained partial regression | 4/5 |
| 111 | 57F, Quebec | GBM | Chemo+RT (concurrent) | IVM 1.5mg/kg/d; MBZ 1500mg/d | 8mo | No recurrence | 4/5 |
| 110 | 50F | GBM | Surgery; RT/chemo discontinued early | IVM+MBZ (dose NS); ketogenic diet | 16mo | No recurrence | 4/5 |
| 109 | 55F, New Jersey | GBM | None | IVM 1.5mg/kg/d; FBZ 1776mg/d→MBZ 1500mg/d | 3.5mo | Partial regression (46%) | 4/5 |
| 108 | 7M, Russia | Cervicomedullary ganglioglioma | None | IVM 1mg/kg/d; MBZ 1000mg/d | 3mo | Stable | 4/5 |
| 107 | 35F, Canada | Astrocytoma Gr.4 | Debulking surgery (prior) | IVM 1.5mg/kg/d; MBZ 1500mg/d | 7mo | No progression | 4/5 |
| 106 | 5M, Switzerland | DIPG | None | IVM 1mg/kg/d; MBZ 1500mg/d; FBZ 1500mg/d | 4mo | Partial regression (26%) | 4/5 |
| 105 | 61F, Kentucky | Oligodendroglioma Gr.2 | None | IVM 36mg/d; FBZ 1500mg/d | 5mo | Partial regression (mild) | 4/5 |
| 104 | 57M, Florida | GBM | Surgery | Not specified | ~4mo | Complete response (patient account) | 4/5 |
| 103 | 51M, Toronto | GBM | Chemo+RT (completed prior) | IVM 1.5mg/kg/d; MBZ 1500mg/d | 6mo | Partial regression, attributed by oncologist to prior chemo/RT | 4/5 |
| 102 | 66M, Ontario | GBM (unmethylated) | None | IVM 168mg/d; MBZ 1500mg/d; melatonin | 5mo | No recurrence | 4/5 |
| 101 | 74M, Canada | GBM | Chemo+RT (concurrent) | IVM 1.5mg/kg/d; MBZ 1500mg/d; CBD | 3–4mo | No abnormal MRI changes | 4/5 |
| 100 | NS, Brazil | Brain cancer, NS | NS | IVM+MBZ+methylene blue | NS | Complete response (minimal detail) | 5 |
| 99 | 36F, California | Multifocal astrocytoma Gr.4 | None | IVM 1mg/kg/d; MBZ 1500mg/d | 2mo | Stable to shrinking | 4/5 |
| 98 | NS | Stage 4 brain cancer | RT+chemo (ongoing) | Recommended only; not confirmed initiated | N/A | No outcome reported | 5 |
| 97 | 41M, Ontario | Oligodendroglioma Gr.3 | Partial resection; declined chemo/RT | IVM 1→2mg/kg/d; FBZ 888mg/d | 3mo | Complete response (residual not found) | 4/5 |
| 96 | Male, NS | GBM | 1 round chemo+RT (ongoing) | IVM+FBZ (dose NS) | NS | Improvement reported (vague) | 5 |
NS = not specified in source. IVM = ivermectin; MBZ = mebendazole; FBZ = fenbendazole; RT = radiotherapy; TMZ = temozolomide. †Case 124: source header and narrative text describe different patients (pediatric medulloblastoma vs. adult oligodendroglioma); narrative content is reported here, and the discrepancy is unresolved in the original source.
Table 2. Independently published retrospective cohort.
| Study | N | Design | Regimen | Outcome | Evidence Level |
|---|---|---|---|---|---|
| METRICS4 | 95 | Retrospective cohort, added to SOC | Mebendazole 100mg/d + atorvastatin ≤80mg/d + metformin ≤1000mg/d + doxycycline 100mg/d | Median survival ~15→27 months vs. benchmark | 3–4 |
3.2 Aggregate outcome distribution (n=38). Complete response, 7 cases (18%); partial regression, 13 cases (34%); stable/no progression, 17 cases (45%); no outcome reported, 1 case (3%). Thirty-four of 38 cases (89%) originate from a single physician's social media/Substack channel.
4. Discussion
The mechanistic rationale for ivermectin and mebendazole in glioma is grounded in preclinical work showing effects on cancer stem cell viability, microtubule assembly, and pathways implicated in GBM recurrence.2,3 The METRICS cohort provides the only case-level dataset here with a defined denominator, protocol, and survival benchmark, and reports a clinically meaningful survival difference; it is nonetheless retrospective, non-randomized, and evaluates a four-drug combination rather than mebendazole in isolation, so mebendazole's independent contribution cannot be determined from it.
The 38 individual cases cannot be interpreted as evidence of efficacy. A 97% favorable-outcome rate in a disease with a median survival under 15 months is not a plausible treatment effect size for any single intervention reported through this channel; it is the expected signature of a dataset built entirely from self-selected, publicly shared success stories, with no mechanism for unfavorable or fatal outcomes to appear. Roughly half of cases involved concurrent conventional treatment, which independently affects survival and radiographic response and cannot be partitioned out of the reported result.
Despite these promising results, resistance to the COC Protocol has been reported as well. The core problem lies in the nature of Cancer Stem Cells (CSCs): these cells are remarkably adaptable. When placed under primarily metabolic pressure, CSCs exploit alternative fuel sources and, given enough time, appear to reliably escape any single-axis metabolic attack.
Building a more powerful, resistance-prevention protocol requires a broader strategy — one that targets far more than cancer’s metabolism alone.
Cancer cells can evade treatment by switching fuel sources — shifting from glucose to glutamine or even lipid metabolism. The COC 4-Drug Protocol has additional drawbacks worth noting. Doxycycline, at standard dose, disrupts the gut microbiome, reducing the effectiveness of agents like Keytruda and Paclitaxel. Atorvastatin carries known risks of liver and muscle toxicity.
The COC protocol (Care Oncology Clinic) relies on Doxycycline and Atorvastatin, which act as metabolic suppressors but have only limited activity to block the fundamental CSC pathways (Wnt, Notch, Hedgehog) that allow cancer stem cells to survive and mutate. In contrast, the RESET-5 protocol targets these crucial pathways more directly.
A critical flaw of the COC protocol is the use of Doxycycline, a broad-spectrum antibiotic that induces severe gut dysbiosis and destroys the microbiome necessary for natural immune surveillance.
The RESET-5 protocol does not contain an antibiotic. SFN and AGE act as powerful, targeted prebiotics that significantly increase populations of Lactobacillus, Bifidobacterium, and Akkermansia.
Multiple high-impact studies have shown that patients with a diverse, favorable gut microbiome experience substantially better response rates and longer survival on PD-1/PD-L1 therapies compared to those with antibiotic-induced dysbiosis.
This native cultivation ensures the gut-immune axis is robustly activated, significantly priming the immune system for CD8+ T-cell infiltration and increasing the efficacy of standard immunotherapies like Keytruda. The microbiome effect is one of the most consistent predictors of PD-1 success across studies.
Atorvastatin carries significant risks of hepatotoxicity and myopathy. Long-term Doxycycline suppresses bone marrow function and strains the kidneys.
The RESET-5 protocol replaces these with highly tolerated phytocompounds and anthelmintics.
SFN and AGE actively protect the liver and bone marrow from chemotherapy-induced toxicity by neutralizing systemic free radicals. Mebendazole and Ivermectin have extensive safety records allowing for continuous use, even in elderly or renally compromised patients.
For brain cancers like Glioblastoma, Ivermectin, SFN, and Mebendazole are highly lipophilic and easily cross the blood-brain barrier. Once inside the brain, they halt tubulin formation and epigenetically reset the neurological stem cells responsible for disease recurrence.
5. Limitations
- Selection and survivorship bias: cases were not ascertained systematically; only outcomes the reporting party chose to share are represented.
- No independent verification: imaging findings, dosing, and outcomes are as relayed by patients/families to a single third party, without medical record confirmation.
- Confounding: concurrent or recent conventional treatment is present in approximately half of cases, precluding attribution of outcome to the repurposed agents.
- No comparator group and no standardized follow-up interval or imaging protocol across cases.
- Single-source dominance: the large majority of cases originate from one individual's public posts, limiting independence of observations.
- Regulatory status: neither agent is FDA-approved for any oncologic indication, and major oncology bodies do not currently recommend either outside of a clinical trial for glioma.
6. Conclusion
This compilation of more than 100 compelling case reports from 2025 and 2026, primarily shared by Dr. William Makis and the METRICS study, illuminates the transformative potential of ivermectin and mebendazole as repurposed adjunctive therapies for aggressive brain cancers such as glioblastoma multiforme and astrocytoma—conditions notorious for their resistance to standard treatments and high recurrence rates.
Nevertheless, while these anecdotal triumphs—backed by MRI evidence and oncologist astonishment—signal a paradigm shift in brain cancer management, they remain observational and demand robust, long-term clinical trials to confirm efficacy, safety, and optimal integration. That said, it may take years before these anti-cancer agents get into mainstream medical journals, as bold results often trigger powerful pushback. The biggest confirmation may not come from top journals but from a grassroots movement of patients and doctors who have proven results.
Disclosures
No external funding was received for this compilation. This manuscript has not undergone external peer review and should not be cited as a peer-reviewed publication. It is not medical advice; treatment decisions for brain tumors should be made with a qualified oncologist.
References
- Median survival estimates for glioblastoma multiforme following standard-of-care treatment. StatPearls / NCBI Bookshelf.
- Benzimidazoles induce concurrent apoptosis and pyroptosis of human glioblastoma cells via arresting cell cycle. Acta Pharmacol Sin (Nature Publishing Group) 2021.
- Therapeutic potential of repurposed mebendazole, alone and in combination with ONC201, in diffuse midline glioma. Am J Cancer Res 2025.
- Retrospective analysis of a four-drug adjunctive regimen (METRICS study) in glioblastoma. Front Pharmacol 2019 (NCT02201381).
- Case-level source material: OneDayMD, "Ivermectin and Mebendazole for Brain Cancer: A Case Series of 133 Case Reports" (June 2026 update), and the public social media/Substack posts cited therein.
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