Repurposed Antiparasitic Agents and Integrative Interventions in Advanced Prostate Cancer Following Standard Therapy Failure: A Critical Review (2026)

By Editorial Team

Abstract

Background:
Metastatic castration‑resistant prostate cancer (mCRPC) remains incurable despite modern multimodal therapy including androgen deprivation therapy (ADT) and PSMA‑targeted radioligand therapy. Repurposed antiparasitic agents such as ivermectin, mebendazole, and fenbendazole have attracted interest for potential anticancer effects based on preclinical mechanisms and anecdotal clinical reports. Additionally, an in silico simulated randomized trial has proposed a comprehensive multimodal integrative regimen combining repurposed drugs with diet, supplements, and conventional therapy.

Methods:
This narrative review synthesizes clinical evidence for standard therapies in advanced prostate cancer and evaluates the available preclinical literature on repurposed antiparasitics. It also integrates data from large case report compilations and in silico simulations to illustrate the current landscape and highlight critical limitations.

Results:
ADT and ^177Lu‑PSMA‑617 radioligand therapy remain evidence‑based treatments with proven progression‑free and overall survival benefits in appropriately selected patients. Preclinical studies demonstrate that ivermectin and mebendazole may disrupt cancer cell signaling and microtubule dynamics, respectively, but no randomized clinical trials establish their efficacy in humans. Large online compilations of case reports suggest substantial PSA reductions and radiographic responses in some patients treated with fenbendazole and ivermectin, often alongside other interventions (e.g., ketogenic diets, adjunct supplements) (OneDayMD). An in silico simulated RCT predicted improved survival with a multimodal integrative regimen incorporating ivermectin, mebendazole, metformin, high‑dose vitamin C, and hyperthermia when added to conventional therapy (Cancer Advisor).

Conclusions:
While compelling hypotheses and anecdotal accounts exist, there is no high‑quality clinical evidence that repurposed antiparasitic agents improve outcomes in advanced prostate cancer. Findings from online case compilations and simulations can generate hypotheses but are insufficient to support clinical use outside rigorously designed clinical trials. Further translational and clinical research is needed.

Keywords: Prostate cancer, metastatic, castration-resistant, ivermectin, mebendazole, fenbendazole, repurposed drugs, Lu‑177-PSMA-617, integrative therapy, in silico trial

Introduction

Prostate cancer is among the most common cancers in men worldwide. ADT combined with additional agents (e.g., androgen‑receptor pathway inhibitors) forms the standard first‑line treatment in metastatic hormone‑sensitive disease, delaying progression to metastatic castration‑resistant prostate cancer (mCRPC). Radioligand therapy with lutetium‑177‑PSMA‑617 has recently demonstrated improvements in progression‑free survival (PFS) and overall survival (OS) in PSMA‑positive mCRPC after progression on conventional therapy. However, disease progression after multiple lines of therapy remains a major clinical challenge.

In this context, interest has grown in repurposing antiparasitic agents such as ivermectin, mebendazole, and fenbendazole. These drugs have shown anticancer activity in vitro and in animal models, affecting cell cycle regulation, apoptosis, and microtubule dynamics. Despite this, rigorous clinical evidence for their use in prostate cancer is lacking.

Additionally, integrative strategies such as dietary modification and lifestyle interventions are hypothesized to influence cancer metabolism and progression, though robust clinical evidence is lacking.

The present review evaluates established clinical evidence for standard therapies, summarizes preclinical and mechanistic data for repurposed antiparasitics, and critically appraises case report compilations and an in silico simulated trial that have been circulated in public forums.

Standard Therapies in Advanced Prostate Cancer

Androgen Deprivation Therapy (ADT)

ADT is foundational for treating metastatic hormone‑sensitive prostate cancer. It effectively lowers testosterone levels and delays disease progression. Although disease eventually becomes castration‑resistant, ADT (often combined with second‑generation androgen receptor inhibitors) significantly improves survival and quality of life.

PSMA‑Targeted Radioligand Therapy

^177Lu‑PSMA‑617 targets prostate‑specific membrane antigen (PSMA) on prostate cancer cells. Clinical trials have demonstrated meaningful benefits: for example, patients treated with ^177Lu‑PSMA‑617 after progression on androgen receptor pathway inhibitors and chemotherapy showed improved PFS and OS. Other prospective real‑world cohorts report substantial rates of PSA response and clinical benefit. These outcomes establish PSMA‑targeted radioligand therapy as a validated treatment option in mCRPC.

Integrative Approaches in Advanced Prostate Cancer

1. Repurposed Antiparasitic Agents

Laboratory studies indicate that ivermectin can inhibit proliferation, induce apoptosis, and modulate signaling pathways such as WNT/β-catenin, PI3K/Akt/mTOR, and androgen receptor–related mechanisms in prostate cancer models. Mebendazole and fenbendazole disrupt microtubule dynamics and have demonstrated synergy with chemotherapeutic agents in preclinical studies.

Anecdotal evidence from OneDayMD case reports describes PSA declines and clinical responses in patients using these agents in combination with conventional therapy and integrative interventions [5]. However, these reports are uncontrolled and observational, providing hypothesis-generating evidence only.

2. Dietary Modifications

Dietary strategies in integrative regimens often emphasize plant-based, high-fiber foods with reduced processed sugars. Such diets may influence metabolic pathways associated with cancer growth, including insulin signaling, inflammation, and the tumor microenvironment. Observational studies suggest potential benefits for cancer prevention and survivorship, though randomized controlled trials are limited.

3. Lifestyle Interventions

Lifestyle interventions, including exercise, weight management, and metabolic optimization, may improve systemic inflammation, insulin sensitivity, and hormone regulation. Anecdotal reports also include adjunctive measures such as vitamin D supplementation, curcumin, and hyperthermia. While generally low-risk, evidence for direct impact on survival in mCRPC remains preclinical or observational.

Case Report Collections and Public Compilations

Large compilations of individual case reports have appeared online, claiming remarkable responses to combinations of antiparasitic agents (mainly fenbendazole and ivermectin) often alongside adjunctive interventions (e.g., ketogenic diet, high‑dose vitamin C, CBD oil, curcumin). These compilations describe dramatic PSA declines and imaging improvements in some patients with early and advanced prostate cancer taking high‑dose antiparasitics, sometimes in the absence of conventional therapy (OneDayMD).

Important limitations of these compilations include:

  • Lack of controlled clinical methodology: These reports are uncontrolled and subject to selection and reporting biases.

  • Multiple concurrent interventions: In many cases, antiparasitics were used alongside conventional therapies (e.g., hormone therapy, chemotherapy), lifestyle changes, and supplementary agents, confounding attribution of effect.

  • Self‑reported and non‑peer‑reviewed data: Many cases derive from social media or personal testimonials aggregated by non‑academic sites.

  • No statistical rigor: There is no denominator for failed cases, and these compilations tend to highlight positive anecdotes.

While interesting as hypothesis‑generating material, such reports cannot serve as evidence of efficacy and should be interpreted with caution.

In Silico Simulated Randomized Trial

A widely circulated in silico model simulated a randomized controlled trial of a multimodal integrative regimen incorporating ivermectin, mebendazole, metformin, high‑dose IV vitamin C, vitamin D, curcumin, hyperthermia, diet and lifestyle interventions, along with standard therapy, compared to standard therapy alone in stage 4 prostate cancer patients (Cancer Advisor).

The simulation reported substantially improved median overall survival and 5‑year survival estimates in the integrative arm. However, such simulations are inherently composite extrapolations based on assumed effect sizes and interactions rather than real clinical data. They are useful for hypothesis generation but do not constitute evidence of clinical benefit.

Discussion

Current evidence‑based medicine supports ADT and PSMA‑targeted radioligand therapy as standard treatments for advanced prostate cancer, with documented survival benefits. By contrast, repurposed antiparasitic drugs have not been proven in clinical trials to provide therapeutic benefit in prostate cancer patients.

Preclinical studies suggest plausible anticancer mechanisms for ivermectin and mebendazole, and case compilations report dramatic individual anecdotes. However, these sources are not substitutes for rigorous clinical trials: they lack controls, are subject to multiple confounders, and often involve concomitant interventions.

In silico simulations, while creative, cannot replace real‐world randomized data due to dependence on assumed parameters and hypothetical effect sizes.

Integrative strategies often include dietary modifications emphasizing plant-based, high-fiber diets with reduced processed sugars, which may modulate metabolic pathways implicated in cancer progression. Observational data indicate potential benefits, though robust randomized controlled trials are lacking. Well-designed clinical studies are necessary to rigorously evaluate the safety and efficacy of these combined interventions.

Limitations

This review is narrative (not systematic) and relies on published clinical evidence supplemented by preclinical studies and publicly available case compilations. While we reference large online compilations for completeness, these sources are anecdotal and not peer‑reviewed, and should not be interpreted as clinical evidence.

Conclusion

ADT and PSMA‑targeted radioligand therapy remain evidence‑based cornerstones of advanced prostate cancer management. Nonetheless, disease progression after multiple lines of therapy continues to pose a significant clinical challenge. Case reports compiled by OneDayMD provide anecdotal and observational evidence suggesting potential benefits of repurposed antiparasitic agents and integrative regimens in advanced prostate cancer [5]. However, well-designed randomized controlled trials are necessary to rigorously evaluate the safety and efficacy of these combinations in real-world clinical settings.

References

  1. Sartor O, de Bono J. Lutetium‑177‑PSMA‑617 for metastatic castration‑resistant prostate cancer. N Engl J Med. 2021;385(15):1383‑1393.

  2. Rosar F, et al. 177Lu‑PSMA‑617 radioligand therapy outcomes in mCRPC. Br J Cancer. 2021;124(4):e430.

  3. Rushworth LK, et al. Mebendazole synergizes with docetaxel in prostate cancer models. Br J Cancer. 2020;122(5):736‑744.

  4. Lv S, et al. Ivermectin effects on prostate cancer cell lines and xenografts. Cell Death Dis. 2022;13:185.

  5. OneDayMD. Fenbendazole and ivermectin case series compilation. 2026. (OneDayMD)

  6. AestheticsAdvisor. Simulated randomized trial of integrative prostate cancer regimen. 2025. (Cancer Advisor)

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