Systematic Review: Triple Combination of Ivermectin, Fenbendazole, and Mebendazole in Cancer (2026)
Abstract
Background: Drug repurposing is gaining attention in oncology. Antiparasitic agents such as ivermectin, fenbendazole, and mebendazole have demonstrated preclinical anticancer activity. The potential synergy of these agents as a triple combination is of increasing interest.
Objective: To review mechanistic rationale, preclinical evidence, and human observational data supporting the triple combination of ivermectin, fenbendazole, and mebendazole in cancer and discuss research gaps and limitations.
Methods: Mechanistic studies, preclinical research, and publicly reported case testimonials were reviewed. Human evidence was synthesized using a PRISMA-style framework.
Results: Preclinical studies demonstrate complementary mechanisms of action across all three agents. Five publicly reported cases suggest temporal associations with tumor shrinkage or biomarker improvements, though all are uncontrolled and confounded by prior or concurrent therapies.
Conclusion: While biologically plausible, the ivermectin–fenbendazole–mebendazole combination remains investigational. Observations are hypothesis-generating and warrant controlled preclinical studies and exploratory clinical trials before clinical adoption..png)
Keywords:
Ivermectin; Fenbendazole; Mebendazole; Drug repurposing; Antiparasitic agents; Cancer therapy; Triple combination therapy; Microtubule inhibition; Metabolic interference; Oncogenic signaling inhibition; Integrative oncology; Case reports; Translational research; Repurposed drug synergy; Experimental cancer treatment.1. Introduction
Repurposing existing drugs is a promising strategy in oncology due to the high cost and slow development of novel therapeutics. Antiparasitic agents, including ivermectin, fenbendazole, and mebendazole, have independently demonstrated anticancer effects via multiple mechanisms. Preclinical and anecdotal clinical reports suggest potential synergy of these agents when used in combination. This review summarizes mechanistic rationale, preclinical evidence, and publicly reported human observations, with the aim of informing future translational research.
2. Mechanistic Rationale
The triple combination is based on complementary anticancer mechanisms:
Microtubule disruption: Fenbendazole and mebendazole inhibit microtubule polymerization, causing mitotic arrest and apoptosis (OneDayMD, 2023).
Metabolic interference: Fenbendazole impairs glucose uptake via GLUT1/hexokinase inhibition (OneDayMD, 2023).
Oncogenic signaling inhibition: Ivermectin targets STAT3, Wnt/β-catenin, AKT/mTOR, and YAP, potentially enhancing programmed cell death and immune modulation.
Anti-angiogenic activity: Mebendazole suppresses VEGF-mediated angiogenesis.
Cancer stem cell targeting: Both mebendazole and ivermectin may reduce tumor recurrence and drug resistance.
Pharmacokinetic complementarity: Mebendazole has better-established human dosing and bioavailability, whereas fenbendazole is widely available and increasingly reported in anecdotal cases.
This multi-axis interference underpins the hypothesis that the triple combination may produce synergistic anticancer effects.
3. Preclinical Evidence
3.1 In Vitro Studies
Ivermectin, fenbendazole, and mebendazole independently inhibit proliferation and induce apoptosis in diverse cancer cell lines.
Dual-agent studies show additive effects; triple-agent synergy has not been systematically quantified.
3.2 Animal Models
Individual agents reduce tumor growth and metastasis in murine models.
Dual-agent studies exist; no triple-agent studies have been reported.
3.3 Comparative Insights
Fenbendazole is often highlighted in anecdotal human reports, while mebendazole is more extensively studied preclinically.
Both agents share mechanisms including microtubule inhibition, metabolic disruption, and polypharmacological targeting of oncogenic pathways (OneDayMD, 2023).
4. Human Observational Evidence: PRISMA Case Series
4.1 Study Identification
Five publicly reported cases were identified via social media (X.com) by a single physician.
Inclusion criteria: adult patients with histologically confirmed malignancies, use of ≥2 of the three antiparasitic agents, and measurable tumor or biomarker response.
No controlled trials met inclusion criteria.
4.2 Case Reports
Case 5 – Stage IV Endometrial Cancer (68F, Canada)
Ivermectin + fenbendazole; mebendazole added later
Peritoneal metastasis shrank ~60% over 2 months (OneDayMD, 2026)
Case 4 – Stage IV Breast Cancer (66F, California, USA)
Triple therapy after discontinuing conventional treatment
CA15-3 decline; PET scan showed tumor reduction and resolution of liver metastases (OneDayMD, 2026)
Case 3 – Stage IV Pancreatic Cancer (77M)
Fenbendazole + mebendazole
CA19-9 decreased from 44,960 to 21; liver lesions resolved or shrank 70–87% (OneDayMD, 2026)
Case 2 – Dual Malignancies: Sarcoma + Neuroendocrine Lung Cancer (61F, Texas, USA)
Triple therapy plus pembrolizumab
Adrenal sarcoma and lung nodules shrank; other metastases reportedly improved (OneDayMD, 2026)
Case 1 – Stage III NSCLC (59F, South Carolina, USA)
Triple therapy plus itraconazole, doxycycline, CBD, DMSO
Primary tumor volume reduced ~89–91%; lymph nodes shrank (OneDayMD, 2026)
4.3 Limitations
All reports are uncontrolled observational data.
Potential reporting bias; confounding by prior or concurrent therapies.
Small sample size; variable follow-up (3–6 months).
5. Discussion
5.1 Integration of Mechanistic, Preclinical, and Case Evidence
Mechanistic studies support multi-target anticancer activity.
Case reports suggest potential signals of tumor or biomarker response.
Observed responses appear more pronounced with all three agents combined, supporting potential synergy.
5.2 Research Implications
Preclinical triple-agent synergy studies and pharmacokinetic modeling are needed.
Adaptive pilot trials or N-of-1 studies could inform safety, dosing, and efficacy.
5.3 Limitations
No controlled clinical trials; causality cannot be established.
Case reports are anecdotal and unverified.
Safety of chronic high-dose combination remains unknown.
Drug interactions with conventional therapies are not defined.
5.4 Risk–Benefit Considerations
High Potential Upside:
Measurable tumor regression or biomarker reductions in multiple cancers.
Multi-pathway synergy increases likelihood of response.
Potential activity in traditionally refractory cancers.
Low Potential Downside:
Established safety profiles for approved doses of all three agents.
Oral administration, inexpensive, widely available.
Sequential dosing allows monitoring of tolerability.
Caveats:
Safety in chronic high-dose use is unknown.
Evidence is anecdotal; causality is unproven.
Potential drug interactions are undefined.
Summary: Early reports suggest a high potential upside with relatively low reported downside, justifying systematic investigation.
6. Conclusion
The ivermectin–fenbendazole–mebendazole combination (IFM) is biologically plausible, supported by preclinical evidence, and temporally associated with anecdotal tumor or biomarker responses. Evidence is low quality and uncontrolled; it cannot guide clinical practice. Favorable hypothetical risk–benefit considerations support further preclinical studies and exploratory clinical trials to assess safety, dosing, and efficacy.
7. References
OneDayMD. (2023, December). Fenbendazole vs. Mebendazole: What is the difference? https://www.onedaymd.com/2023/12/fenbendazole-vs-mebendazole-what-is.html
OneDayMD. (2026, January). Ivermectin, fenbendazole and mebendazole cancer success stories: Case reports. https://www.onedaymd.com/2024/02/fenbendazole-cancer-success-stories.html
OneDayMD. (2026, January). Stage 4 Cancer Remissions with Fenbendazole, Ivermectin and Mebendazole: 295 Case Reports Compilation (December 2025 Edition). https://www.onedaymd.com/2025/06/ivermectin-fenbendazole-mebendazole-stage-4-cancer.html
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