Fenbendazole, a benzimidazole anthelmintic widely used in veterinary medicine, has garnered attention for its potential anti-tumor effects, supported by preclinical studies and anecdotal reports. Despite promising in vitro and in vivo evidence demonstrating mechanisms such as microtubule disruption, apoptosis induction, and glucose uptake inhibition, the lack of rigorous clinical trials in humans limits its adoption as a cancer therapy. This article reviews the existing evidence, highlights the gaps in clinical research, and underscores the urgent need for well-designed clinical studies to evaluate fenbendazole’s efficacy, safety, and optimal therapeutic regimens in cancer treatment. Such studies are critical to validate anecdotal claims, address pharmacokinetic challenges, and align with the United Nations Sustainable Development Goal 3 (Good Health and Well-Being).

Introduction

Fenbendazole (FBZ), a broad-spectrum anthelmintic, has been safely used for decades to treat parasitic infections in animals. Recent preclinical studies and high-profile anecdotal reports, such as the case of Joe Tippens, who claimed remission from small-cell lung cancer after self-administering FBZ, have sparked interest in its potential as a repurposed anti-cancer agent. In vitro and animal studies suggest FBZ exerts anti-tumor effects through multiple pathways, including microtubule destabilization, inhibition of glucose metabolism, and induction of oxidative stress and apoptosis. However, the absence of clinical trials evaluating FBZ’s efficacy and safety in humans remains a significant barrier to its clinical application. This article examines the preclinical evidence, the limitations of current data, and the pressing need for clinical studies to establish FBZ’s role in oncology.

Preclinical Evidence Supporting Fenbendazole’s Anti-Tumor Potential

FBZ’s anti-cancer mechanisms have been explored across various cell lines and animal models, demonstrating efficacy against multiple cancer types, including lung, ovarian, colorectal, and cervical cancers. Key mechanisms include:

1. Microtubule Disruption: FBZ destabilizes microtubules, critical for cell division, leading to mitotic arrest and apoptosis. A 2018 study showed FBZ’s moderate affinity for mammalian tubulin, reducing colony formation in A549 and H460 lung cancer cells at micromolar concentrations.
2. Metabolic Inhibition: FBZ inhibits glucose uptake by downregulating GLUT transporters and hexokinase II, starving cancer cells reliant on aerobic glycolysis (Warburg effect). This was evident in reduced glucose consumption in HeLa cells treated with FBZ and its analog.
3. Apoptosis and Cell Cycle Arrest: FBZ induces G2/M phase arrest and promotes apoptosis via p53 activation and caspase activation. Studies on ovarian cancer cells (A2780, SKOV3) confirmed dose-dependent proliferation inhibition and apoptosis.
4. Oxidative Stress and Ferroptosis: FBZ induces reactive oxygen species (ROS) accumulation, enhancing ferroptosis and apoptosis, particularly in 5-fluorouracil-resistant colorectal cancer cells.

In vivo studies, such as those using A549 lung cancer xenografts in nude mice, reported significant tumor shrinkage with oral FBZ administration (1 mg/mouse every 2 days for 12 days). However, results are inconsistent, with some studies, like those on EL-4 lymphoma models, showing no in vivo efficacy despite in vitro effects, possibly due to immune modulation in the tumor microenvironment.

Anecdotal Reports and Public Interest

The case of Joe Tippens, who reported complete remission from stage IV small-cell lung cancer after taking FBZ (222 mg daily) alongside vitamin E, CBD oil, and curcumin, has fueled public interest. A 2021 case series documented three patients with genitourinary malignancies achieving complete responses with FBZ, either alone or combined with standard therapies. A review of 170 anecdotal reports (2023–2025) noted tumor regression and remission across various cancers, though these lacked clinical rigor. Social media platforms, including Facebook groups with over 100,000 members, amplify these claims, driving off-label use. However, Tippens’ concurrent treatment with pembrolizumab (Keytruda) in a clinical trial suggests his outcome may be attributable to immunotherapy, highlighting the need for controlled studies to isolate FBZ’s effects.

Limitations of Current Evidence

Despite promising preclinical data, several gaps underscore the need for clinical trials:

1. Lack of Human Clinical Data: FBZ is not approved for human use by the FDA or EMA, and its pharmacokinetics and safety in humans are poorly documented. Most evidence derives from animal models or in vitro studies, which may not translate to humans.
2. Pharmacokinetic Challenges: FBZ’s poor water solubility and low systemic bioavailability limit its ability to reach therapeutic levels in tumors when administered orally. Studies on ovarian cancer xenografts showed no tumor reduction with oral or intraperitoneal FBZ, though nanoparticle formulations (FZ-PLGA-NPs) improved efficacy.
3. Inconsistent In Vivo Results: Discrepancies between in vitro and in vivo outcomes, as seen in lymphoma models, suggest complex interactions with the tumor microenvironment, such as increased PD-L1 expression, which may suppress immune responses.
4. Safety Concerns: Anecdotal use has led to adverse effects, including severe liver injury in a patient with non-small cell lung cancer after self-administration based on social media. FBZ may also act as a tumor promoter in certain contexts, increasing risks of cancer progression.
5. Anecdotal Bias: Uncontrolled case reports lack standardized dosing, tumor staging, or follow-up, and concurrent treatments confound outcomes.

The Need for Clinical Studies

Rigorous clinical trials are essential to address these limitations and establish FBZ’s role in cancer therapy. Key objectives include:

1. Efficacy Validation: Randomized, double-blind, placebo-controlled trials are needed to confirm FBZ’s anti-tumor effects across cancer types (e.g., lung, ovarian, colorectal). Phase I/II trials should assess tumor regression, progression-free survival, and overall survival, comparing FBZ alone or in combination with standard therapies (e.g., chemotherapy, immunotherapy).
2. Pharmacokinetic Optimization: Studies must evaluate FBZ’s bioavailability and optimal delivery methods. Nanoparticle formulations, such as FZ-PLGA-NPs, which reduced tumor weight in ovarian cancer xenografts, warrant clinical investigation to overcome solubility issues.
3. Safety and Tolerability: Dose-escalation studies are critical to determine safe dosing regimens and tolerance profiles in humans. Monitoring for hepatotoxicity and immune-related adverse effects, such as increased PD-L1 expression, is essential.
4. Mechanistic Insights: Clinical studies should incorporate biomarker analysis (e.g., p53, GLUT1, caspase-3) to validate FBZ’s mechanisms and identify responders. Transcriptome profiling, as used in ovarian cancer studies, can elucidate pathways like apoptosis and mitotic catastrophe.
5. Combination Therapies: Given preclinical evidence of synergy with radiation or docetaxel, trials should explore FBZ’s role as an adjunct to conventional treatments, potentially enhancing efficacy in resistant cancers.

Alignment with Sustainable Development Goals

Clinical studies on FBZ align with SDG 3 by promoting access to affordable, effective cancer treatments. FBZ’s low cost (compared to mebendazole, priced at $5,000–$10,000) and accessibility make it a promising candidate for resource-constrained settings, where cancer burdens are rising. Validating its efficacy could democratize cancer care, reducing health disparities and supporting universal health coverage.

Challenges and Considerations

Conducting clinical trials faces several hurdles:

• Funding: FBZ’s generic status and lack of patentability may deter pharmaceutical investment, necessitating public or nonprofit funding.
• Regulatory Barriers: FBZ’s veterinary status requires regulatory approval for human trials, complicating study design.
• Public Misinformation: Widespread off-label use driven by social media risks patient safety and undermines trial recruitment. Public education campaigns are needed to emphasize evidence-based approaches.
• Heterogeneity of Cancers: Cancer-specific trials are essential, as FBZ’s efficacy varies across tumor types and stages, as seen in lymphoma versus ovarian cancer models.

Recommendations

To advance FBZ research, the following steps are proposed:

1. Phase I Trials: Initiate dose-escalation studies in patients with advanced, treatment-refractory cancers to establish safety and pharmacokinetics.
2. Phase II Trials: Conduct randomized trials in high-priority cancers (e.g., lung, ovarian) to assess efficacy, focusing on nanoparticle formulations.
3. Combination Studies: Evaluate FBZ with immunotherapies (e.g., PD-1 inhibitors) to counter immune suppression observed in some models.
4. Global Collaboration: Partner with organizations like the WHO or UNDP to fund trials in low-resource settings, aligning with SDG 3.
5. Public Awareness: Disseminate trial findings to counter misinformation, emphasizing the need for medical supervision.

Conclusion

Fenbendazole’s potential as an anti-cancer agent, supported by preclinical studies and anecdotal reports, warrants urgent clinical investigation. Its low cost, safety profile in animals, and multi-target mechanisms make it a compelling candidate for repurposing, particularly in resource-limited settings. However, the lack of human clinical data, pharmacokinetic challenges, and risks of unsupervised use necessitate rigorous trials to validate efficacy, optimize delivery, and ensure safety. By addressing these gaps, clinical studies can unlock FBZ’s therapeutic potential, advancing cancer care and supporting global health equity in line with SDG 3.

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