Dr William Makis Ivermectin Protocol 2026: Complete Protocol Guide + Real-World Patient Outcomes
A comprehensive synthesis of Dr Makis's clinical dosing regimens, benzimidazole combination strategies, the 2026 Hulscher observational cohort, pharmacokinetic rationale, safety monitoring requirements, and anonymised patient outcome data — presented with evidence grading.
Background: Dr William Makis MD (McGill Medicine; 110+ peer-reviewed publications) has treated cancer patients using repurposed antiparasitic agents since 2023, publicly documenting protocols and outcomes via Substack and X (@MakisMD). His approach centres on high-dose ivermectin combined with benzimidazoles and metabolic interventions, customised by cancer type and stage.
Purpose: This continuously updated review synthesises Dr Makis's published protocols, the April 2026 Hulscher et al. prospective observational cohort (n=197), controlled trial data on mebendazole, known mechanisms of action, drug interaction considerations, and safety monitoring requirements.
Evidence Level: Most clinical data are anecdotal case reports and observational cohorts. The only Phase 2 RCT to date (mebendazole + FOLFOX4 in colorectal cancer, Life Sciences 2022) does not cover the full combination protocol. No Phase 3 RCT exists for ivermectin as a standalone oncological agent as of June 2026. All protocols require physician supervision.
Section 1Who Is Dr William Makis
Dr William Makis is a Canadian-trained physician and former oncologist who graduated from McGill University Faculty of Medicine and has authored over 110 peer-reviewed publications across nuclear medicine, oncology, and diagnostic imaging. He currently practises in Florida, USA.
Since 2023, Dr Makis has treated a substantial volume of cancer patients — predominantly Stage 3 and Stage 4 — using metabolic-based approaches combined with repurposed antiparasitic drugs. He documents outcomes publicly on Substack and X (@MakisMD), including anonymised patient updates, treatment progress reports, and dosing discussions. A number of these cases have been compiled into observational reports co-authored with other investigators.
His broader framework — which he terms a Metabolic-Immune Cancer Protocol — integrates benzimidazoles, ivermectin, high-dose Vitamin D, intravenous Vitamin C, a ketogenic diet, methylene blue, and berberine. Ivermectin is the anchor of this combination.
Section 2Mechanisms of Action — Why Ivermectin in Cancer?
Ivermectin's potential oncological relevance stems from several mechanistic pathways identified in preclinical research. These are not proven in human clinical trials but provide the scientific rationale for the protocols below.
Established Preclinical Mechanisms
P-glycoprotein (P-gp / ABCB1) inhibition. Ivermectin inhibits P-glycoprotein, an ATP-dependent efflux pump that cancer cells overexpress to expel chemotherapy agents. This may enhance intracellular drug accumulation and reverse multi-drug resistance — a key motivation for combining ivermectin with conventional chemotherapy.
Wnt/β-catenin pathway suppression. Ivermectin has been shown in preclinical models to downregulate Wnt/β-catenin signalling, a pathway central to cancer stem cell (CSC) self-renewal. CSCs are hypothesised to drive relapse and metastasis. This makes ivermectin particularly relevant in tumours with high CD44⁺/CD24⁻ CSC fractions (e.g., triple-negative breast cancer, colorectal cancer).
NF-κB suppression. NF-κB drives survival, proliferation, and inflammatory signalling in many tumour types. Ivermectin has demonstrated NF-κB inhibitory effects in preclinical models, potentially reducing tumour-permissive inflammation.
Mitochondrial membrane disruption. At high concentrations, ivermectin acts on the Cl⁻ ion channel PAK1/chloride channel and may disrupt mitochondrial membrane potential in cancer cells, promoting apoptosis — particularly in cells reliant on oxidative phosphorylation.
Immunomodulation. Some preclinical data suggest ivermectin may enhance T-cell and NK-cell activity in the tumour microenvironment, consistent with its synergy with immunotherapy in selected patient reports.
Why Combine with Benzimidazoles?
Fenbendazole and mebendazole target tubulin polymerisation via a distinct binding site (colchicine-binding domain) compared to conventional taxanes. Their combination with ivermectin provides mechanistic complementarity: ivermectin targets P-gp, Wnt/β-catenin, and NF-κB; benzimidazoles target the cytoskeleton and glucose metabolism (via GLUT-4 suppression and AMPK activation). Preclinical combination index (CI) values below 1.0 for several analogues suggest synergistic rather than merely additive effects.
Section 3Dr Makis's Core Ivermectin Cancer Protocols (2025–2026)
The protocols below are compiled from Dr Makis's Substack, X posts, and observational publications through May 2026. They represent his clinical framework as publicly documented — they are not formal guidelines from any regulatory body or oncology society.
Standard Protocol
Aggressive / High-Grade Protocol
Low-Dose Ivermectin + High-Dose Benzimidazole
Maintenance / Remission Protocol
Section 4Core Protocol Rules (2025–2026)
Regardless of which protocol applies, Dr Makis emphasises the following universal rules across his documented cases:
- Take with a fatty meal. Ivermectin is highly lipophilic. Bioavailability increases 2–3× when taken with a high-fat meal. This is critical at oncological doses where adequate tissue penetration is required.
- Use only human pharmaceutical-grade tablets. Use 12 mg tablets from a licensed pharmacy. Veterinary ivermectin paste or paste formulations differ significantly in concentration, inactive ingredients, and purity standards — do not substitute.
- Monitor liver function and renal function. LFTs (ALT, AST, GGT, ALP, bilirubin) and renal function (creatinine, eGFR) every 4–6 weeks during standard dosing; every 2–3 weeks during combination benzimidazole use or Protocol 2.
- Combine with a ketogenic or low-carbohydrate diet. Glucose restriction is central to the metabolic rationale. A ketogenic diet (Glucose-Ketone Index ≤ 2.0) or intermittent fasting is used alongside the drug protocol for potential synergistic metabolic pressure on tumour cells.
- Liver support: Milk Thistle (silymarin). Silymarin 300–600 mg/day is widely used by patients on this protocol for hepatoprotection. Compatible with the protocol and frequently recommended given the hepatic metabolic load of combined benzimidazoles.
- Topical DMSO on accessible tumours (Protocol 2). DMSO combined topically with ivermectin or benzimidazoles on superficially accessible lesions may enhance local absorption. Physician guidance required. Not applicable to all patients.
- Never taper abruptly after a major response. In Dr Makis's clinical framework, patients achieving NED transition to the Maintenance Protocol (Protocol 4) rather than stopping treatment — abrupt discontinuation after a good response may risk recurrence, per his documented cases.
- Methylene Blue timing caution. For patients using Methylene Blue (Protocol 2), separate from antioxidants (Vitamin C, NAC, Curcumin) by at least 2 hours. Forcing oxidative phosphorylation while simultaneously providing antioxidant cover may reduce its pro-oxidative anticancer effect.
Section 5Should You Combine Mebendazole with Fenbendazole? 2025–2026 Evidence
A frequently asked question from patients concerns whether combining both benzimidazoles — mebendazole (AM) and fenbendazole (PM) — is appropriate and what the evidence base is.
Preclinical Evidence
Combination index (CI) values below 1.0 have been reported for mebendazole-fenbendazole combinations against several cancer cell lines in vitro, suggesting synergistic rather than merely additive effects. Xenograft reduction rates of 80–90% versus single-agent comparators have been reported in rodent models (Anticancer Research). Distinct but complementary tubulin-binding profiles suggest mechanistic rationale for the pairing.
Clinical Trial Evidence
No RCT has evaluated the combination of ivermectin + mebendazole + fenbendazole as a triplet. Indirect support comes from the mebendazole + temozolomide glioblastoma trial (EClinicalMedicine, 2022) and the Phase 2 mebendazole + FOLFOX4 RCT in colorectal cancer (detailed in Section 7).
Real-World Reports from Dr Makis (2025–2026)
Dr Makis's February 2026 Substack publication, "Triple Combination of Ivermectin, Mebendazole and Fenbendazole for Cancer: 18 Case Reports," describes the following in patients treated with all three agents:
- Pancreatic cancer: 70–87% shrinkage reported using mebendazole AM + fenbendazole PM scheduling
- Breast cancer: NED in 6 weeks (triple combination: ivermectin + mebendazole + fenbendazole)
- 18 case reports across multiple histologies
Section 62026 Hulscher et al. Prospective Observational Cohort
The most systematic real-world dataset to date on the ivermectin + mebendazole combination was published in April 2026 by Hulscher et al. as a peer-reviewed prospective observational study.
Study Overview
Reported Outcomes Breakdown
| Outcome Category | Rate | Interpretation |
|---|---|---|
| No Evidence of Disease (NED) | 32.8% | Complete remission by imaging criteria |
| Tumour Regression | 15.6% | Partial response; measurable reduction |
| Stable Disease | 36.1% | No progression at ≥6 months |
| Clinical Benefit Rate (CBR) | 84.4% | NED + Regression + Stable combined |
| Mild GI Side Effects | 25.4% | Nausea, elevated enzymes; most continued treatment |
Important Methodological Caveats
1. No control group. Without a parallel untreated or standard-of-care arm, it is impossible to attribute outcomes specifically to the drug protocol rather than to concurrent conventional treatment, natural disease course, patient selection, or regression to the mean.
2. Mixed cancer types. Breast, prostate, colorectal, and other histologies are pooled.
3. Concurrent treatments. Many patients were simultaneously receiving conventional oncology treatments (chemotherapy, hormonal therapy, immunotherapy) and diet/lifestyle interventions.
4. Self-reported outcomes. Some outcome data were patient-reported, introducing reporting bias.
Interpretation: This is the largest real-world dataset to date and hypothesis-generating. It justifies rigorous clinical trials. It does not constitute proof of efficacy.
Section 7Phase 2 RCT: Mebendazole in Stage 4 Colorectal Cancer
The strongest controlled trial evidence for a benzimidazole in cancer comes from a Phase 2 randomised controlled trial examining mebendazole added to standard chemotherapy in advanced colorectal cancer, published in Life Sciences (2022).
| Outcome Measure | Control Group (Bevacizumab + FOLFOX4) | Mebendazole Group (+ Mebendazole) | p-value |
|---|---|---|---|
| Overall Response Rate (12 weeks) | 10% | 65% | p < 0.001 |
| Progression-Free Survival | 3 months | 9.25 months | p < 0.001 |
| Tolerability | — | Well tolerated; no additional serious adverse events | — |
Section 8Evidence Hierarchy Summary (June 2026)
| Intervention | Highest Evidence Level | Source / Citation | Strength |
|---|---|---|---|
| Mebendazole + FOLFOX4 (CRC) | Phase 2 RCT | Life Sciences, 2022 | Moderate-High |
| Mebendazole + Temozolomide (GBM) | Phase 1/2 RCT | EClinicalMedicine, 2022 | Moderate |
| Ivermectin + Mebendazole (mixed cancers) | Prospective observational cohort | Hulscher et al., 2026 (n=197) | Low-Moderate |
| Ivermectin + Mebendazole + Fenbendazole | Observational case series | Makis, 2026 (18 cases) | Low |
| Ivermectin alone (multiple cancer types) | Preclinical + anecdotal | Multiple in vitro/in vivo studies | Very Low (Clinical) |
| Fenbendazole alone (multiple cancer types) | Preclinical + anecdotal | No registered RCT | Very Low (Clinical) |
Section 9Real Patient Outcomes: Dr Makis's Practice (2025–2026)
The following cases are drawn from Dr Makis's publicly documented reports on X (@MakisMD) and Substack, 2025–2026. All patients are anonymised. These are anecdotal case reports; outcomes reflect individual patients under direct physician guidance and may not be representative of patients self-managing or following different protocols.
-
Stage 2 TNBC
53-year-old Canadian woman. Triple-Negative Breast Cancer, 7.8 cm tumour. Outcome: cancer-free in 7 months (December 2024 – July 2025).
-
Stage 4 RCC
58-year-old California CEO. Recurrent Stage 4 Kidney (Renal Cell) Cancer. Outcome: tumour necrosis visible on imaging at 10 weeks.
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Stage 4 Lymphoma
70-year-old man (Morocco). Stage 4 Lymphoma. Outcome: complete remission in 2.5 months.
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Stage 4 CRC
39-year-old Texas woman. Stage 4 Colon Cancer with liver metastases. CEA declined from 441 to 21.9 in 4 months.
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Stage 4 RCC
42-year-old woman. Stage 4 Kidney Cancer with lung, liver, and shoulder metastases. Outcome: NED after 1 year.
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Stage 4 Breast
53-year-old UK woman. Stage 4 Breast Cancer, 12 cm tumour. Outcome: 68% shrinkage at 2 months.
-
Stage 3 Ovarian
Patient, Stage 3 Ovarian Cancer. Low-dose ivermectin (12 mg/day, approximately 0.2 mg/kg for a 60 kg individual) combined with concurrent chemotherapy. Outcome: complete resolution at 2 months.
-
Stage 3 Follicular
83-year-old patient. Stage 3 Follicular Lymphoma. Ivermectin 1 mg/kg/day. Outcome: near-total remission at 6 months.
-
Recurrent PCa
54-year-old patient. Recurrent Prostate Cancer. Ivermectin 1.5 mg/kg/day. Outcome: remission at 4 months.
For a broader compilation: Fenbendazole, Ivermectin and Mebendazole Cancer Success Stories: 700+ Case Reports (2026 Edition)
Section 10Frequently Asked Questions: Safety & Drug Interactions
Fenbendazole and mebendazole are both metabolised via CYP2C9/CYP3A4 pathways — the same cytochrome P450 enzymes involved in Capecitabine metabolism. There is a theoretical drug interaction risk that could alter plasma levels of either the repurposed agent or the chemotherapy. No formal pharmacokinetic interaction study exists as of June 2026.
Patients considering this combination should: (1) disclose all medications to their oncologist; (2) increase CBC and LFT monitoring frequency to weekly for the first 4–6 weeks; (3) proceed only under physician supervision with dose adjustments available if adverse effects emerge.
High-dose ivermectin and benzimidazoles are all hepatically metabolised. Patients with pre-existing liver disease (cirrhosis, chronic hepatitis, baseline elevated transaminases) face substantially increased hepatotoxicity risk on any of these agents, and the risk compounds with combination use.
If these agents are considered at all in the context of existing liver disease, this requires: specialist hepatology and oncology co-supervision; significantly lower starting doses with slow up-titration; LFT monitoring every 2–3 weeks; and a clear threshold for dose reduction or discontinuation if ALT/AST rises above 3× the upper limit of normal.
Dr Makis categorises haematological malignancies including lymphoma, leukaemia, and multiple myeloma under Protocol 2 (Aggressive/High-Grade Protocol). Mechanistically, ivermectin's P-glycoprotein inhibition is particularly relevant in haematological cancers where P-gp overexpression is a well-documented mechanism of chemotherapy resistance.
Some case reports in Dr Makis's documented series suggest responses in lymphoma and leukaemia. These remain anecdotal. See dedicated coverage: Ivermectin and Mebendazole in Lymphoma and Leukaemia (February 2026) on Substack.
Several supplements have been reported by patients without adverse events alongside ivermectin and fenbendazole, including: Liposomal Vitamin C and D, Vitamin K, Curcumin, Milk Thistle (silymarin), Vitamin B complex, Turmeric, Magnesium, Krill Oil, and NAC. However, formal pharmacokinetic interaction data is lacking.
Caution is warranted with: (1) St John's Wort — a potent CYP3A4 inducer that could reduce ivermectin plasma levels; (2) grapefruit (high-dose) — a CYP3A4 inhibitor that could increase ivermectin levels; (3) strong antioxidants taken simultaneously with Methylene Blue (see Protocol Rules above).
Always disclose all supplements and herbal preparations to your physician.
Ivermectin has been an approved, widely used antiparasitic for human use since the 1980s (Nobel Prize, 2015). Standard antiparasitic dosing is typically 0.15–0.20 mg/kg as a single dose or short course — substantially lower than the cancer protocol doses above. It is used for conditions including onchocerciasis (river blindness), lymphatic filariasis, strongyloidiasis, and scabies. Consult a physician for appropriate antiparasitic dosing for your region and clinical situation.
Integrative oncologists, functional medicine physicians, and some naturopathic doctors with oncology experience are the most likely practitioners to be willing to supervise and monitor a repurposed-drug protocol alongside conventional care. The FLCCC Alliance (flccc.net) maintains a provider directory of clinicians familiar with repurposed drug protocols. The Wellness Company (TWC) also offers telehealth access to physicians who can prescribe and monitor these agents in the US.
Approach your conventional oncologist as well — even if they are sceptical of the repurposed drugs themselves, they are best placed to order and interpret the oncology imaging and tumour markers needed to evaluate response.
Section 11Where to Obtain Ivermectin and Mebendazole Safely in 2026
Ivermectin and mebendazole are both approved for human use and available in the United States through controlled medical frameworks. The following principles apply regardless of source:
- Human pharmaceutical-grade only. Veterinary ivermectin formulations (paste, injectable) are not appropriate for human use at these doses. Concentration, inactive ingredients, excipients, and purity differ from pharmaceutical tablets.
- Licensed pharmacy dispensing. Ivermectin at oncological doses requires a physician prescription. Compounding pharmacies can produce appropriate-strength formulations (e.g. 12 mg tablets in larger quantities) to a pharmaceutical standard.
- Physician oversight required. A licensed physician must issue the prescription, review baseline bloodwork, and provide ongoing monitoring. Telehealth platforms operating in the US can facilitate this.
- Prescribed by licensed US physicians
- Compounded in US-based pharmacies to pharmaceutical standards
- Quality-tested for purity and consistency
- Standardised dosing with clear physician guidance
The Wellness Company — US-licensed, physician-prescribed
Affiliate Disclosure: OneDayMD has an affiliate relationship with The Wellness Company and may receive compensation from purchases made through this link. This does not influence our editorial content or protocol descriptions.
Section 12Conclusion
Repurposed antiparasitic agents — ivermectin, fenbendazole, and mebendazole — have generated substantial interest in integrative oncology circles, driven by a growing body of preclinical mechanistic data, a Phase 2 RCT demonstrating significant benefit for mebendazole in colorectal cancer, and an increasing number of observational reports from clinicians including Dr Makis.
The 2026 Hulscher et al. cohort (n=197) represents the most rigorous real-world dataset to date and warrants serious attention from oncological researchers. Its 84.4% clinical benefit rate is striking, but must be contextualised by its methodological limitations — principally the absence of a control group and the heterogeneity of concurrent treatments.
The honest synthesis of the current evidence base is this: there is sufficient scientific rationale and observational signal to justify well-designed, adequately powered randomised controlled trials in specific cancer histologies. There is not yet sufficient evidence to recommend these protocols as replacements for established standard-of-care oncology treatment.
For patients facing limited conventional options, or who wish to integrate metabolic approaches alongside standard therapy, these protocols represent a thoughtful framework — provided that physician supervision, regular safety monitoring, and transparent communication with the full oncology team are maintained.
- Ivermectin at 1.0–2.0 mg/kg/day is used in Dr Makis's cancer protocols — well above standard antiparasitic dosing and requiring physician supervision
- The strongest controlled evidence is for mebendazole specifically, not the full combination
- The Hulscher 2026 cohort is hypothesis-generating, not practice-defining
- LFT and renal function monitoring every 4–6 weeks is non-negotiable
- Combination with a ketogenic diet and liver support (silymarin) is standard in Dr Makis's framework
- These protocols are best understood as complementary to, not a replacement for, conventional oncology
ReferencesKey References & Sources
- Hulscher JBF, et al. Prospective observational cohort study of ivermectin and mebendazole in cancer patients (n=197). Journal [PubMed, May 2026]. Available at: OneDayMD summary.
- Sasaki J, et al. Phase 2 randomised controlled trial of mebendazole + bevacizumab + FOLFOX4 in Stage 4 colorectal cancer. Life Sciences. 2022. doi:10.1016/j.lfs.2022.120520
- Makis W. Triple combination of ivermectin, mebendazole and fenbendazole for cancer: 18 case reports. Substack, February 2026. Link
- Scheim DE, et al. Ivermectin for COVID-19: real-world evidence — relevance to cancer mechanisms. Am J Ther. 2022.
- Guerini AE, et al. Mebendazole as a candidate for repurposing in oncology: an extensive review of current literature. Cancers. 2019;11(9):1284.
- Dogra N, et al. Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways. Sci Rep. 2018;8(1):11926.
- Juarez M, et al. Multitarget biological effects of ivermectin in cancer. Pharmacol Res. 2018;136:87–96.
- EClinicalMedicine (2022): Mebendazole + temozolomide in glioblastoma. Available at: PubMed 35747192
Related Articles on OneDayMD
- → Fenbendazole, Ivermectin and Mebendazole: 700+ Case Reports (2026 Edition)
- → Ivermectin, Fenbendazole and Mebendazole: A Peer-Reviewed Summary
- → Ivermectin Dosage Guide for Humans (2026)
- → Best Fenbendazole Dosage for Humans: Safety, Side Effects, and Protocols
- → Repurposed Drugs, Integrative Cancer Care & Precision Oncology 2026
Important Disclaimers
For educational purposes only. This content does not constitute medical advice, diagnosis, or treatment. Ivermectin is used off-label for cancer treatment. Always consult with a qualified physician you trust for decisions about your health and cancer management. Do not self-medicate with ivermectin at oncological doses without appropriate bloodwork and medical supervision, as misuse can cause serious side effects and drug interactions.
FDA / Regulatory disclaimer. Statements on this website have not been evaluated by the Food and Drug Administration. The contents of this website are for educational and informational purposes only and are not intended as a substitute for professional medical advice, diagnosis, or treatment.
Individual results disclaimer. The case reports and outcomes described reflect individual experiences documented by Dr Makis or reported by patients. These experiences may not be representative of all patients. Outcomes depend on many variables including cancer type, stage, comorbidities, concurrent treatments, protocol adherence, and individual pharmacology. Do your own research and consult relevant medical professionals before considering any repurposed drug protocol.
Complementary, not alternative. Cancer care is best delivered through a multi-modal approach with the patient at the centre. Integrating a repurposed drug protocol does not mean rejecting modern oncology — it supplements it. Care should be supervised and coordinated by a primary healthcare provider, oncologist, and integrative medicine physician working together.
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