Joe Tippens : Fenbendazole (Panacur) Cancer Story and Cancer Cure -- DIY: how I defeated cancer with Fenbendazole - Safe-Guard Dewormer Suspension for Beef, Dairy Cattle and Goats, 1000ml

Edmond man says cheap drug for dogs cured his cancer
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  KOCO logoUpdated: 12:04 PM CDT Apr 26, 2019
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EDMOND, Okla. —
When you tell someone a medicine for dogs cured your cancer, you better be ready for some skeptics, but Joe Tippens says it saved his life, and the lives of others.

Now, even cancer researchers are open to the possibility it might be true.

"My stomach, my neck, my liver, my pancreas, my bladder, my bones -- it was everywhere," Tippens said.

Tippens said he was told to go home, call hospice and say his goodbyes two years ago.

The doctors were unanimous, he was going to die of small cell lung cancer.

"Once that kind of cancer goes that far afield, the odds of survival are less than 1 percent, and median life expectancy is three months," Tippens said.

Tippens said he went from 220 pounds to 110.

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"I was a skeleton with skin hanging off of it," he said. "It was difficult."

But that was January of 2017. Today, Tippens is very much alive and what he credits for his survival has doctors scratching their heads, and the rest of us raising eyebrows.

"About half the people think I'm just crazy," he said. "And about half the people want to know more and dig deeper."

Tippens said he received a tip from a veterinarian, of all people. And in his desperation, he turned from people medicine to dog medicine.

Specifically, something you give your dog when it has worms.

"The truth is stranger than fiction, you know?" Tippens said, laughing.

Just three months later, Tippens says, his cancer was gone.

"I'm usually skeptical, and I was and maybe still am about this one," said Stephen Prescott, president of the Oklahoma Medical Research Foundation. "But there's interesting background to this."

Cancer researchers like Prescott are skeptical, but they also are not dismissing this anti-parasitic's potential.

He says Tippens is not the first person to potentially benefit, and not the last.

"Scientists and many credible places have done work on this for years," Prescott said.

But was it the de-wormer, or was it something else?

Tippens took the dog medicine with daily vitamin E supplements and CBD oil.

He was also taking an experimental cancer-fighting drug. But Tippens says out of the 1,100 patients on that clinical trial, he was the only one cleared of cancer.

Tippens says he was saved by the dog de-wormer and he plans to take it for the rest of his life.

"My insurance company spent $1.2 million on me with traditional means before I switched to a $5 a week medicine that actually saved me," he said.

Prescott says he's now working with Tippens to organize a case study.

"We're going to do it and see if we can confirm, in a very rigorous and clinical sort of way, that these patients had that kind of response," Prescott said.

As for Tippens: "I've got over 40 success stories other than me," he said.

He's sharing his story on an online blog that has been read more than 100,000 times. Most of the feedback is positive, or curious.

Some accuse Tippens of giving cancer patients false hope.

"Oh, how do I answer that?" he sighed. "I mean, if I've saved one other person other than me, it's worth it to me."

All we know for sure is that Tippens is alive.

In time, perhaps we'll also know if this medicine made for man's best friend might also be man's newest cancer cure.

Oral Fenbendazole for Cancer Therapy in Humans and Animals
JOLIE NGUYEN, THAI Q. NGUYEN, BO HAN and BA X. HOANG
Anticancer Research September 2024, 44 (9) 3725-3735; DOI: https://doi.org/10.21873/anticanres.17197
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Abstract
Fenbendazole is a benzimidazole anthelmintic agent commonly used to treat animal parasitic infections. In humans, other benzimidazoles, such as mebendazole and albendazole, are used as antiparasitic agents. Since fenbendazole is not currently approved by the FDA or EMA, its pharmacokinetics and safety in humans have yet to be well-documented in medical literature. Despite this, insights can be drawn from existing in vitro and in vivo animal studies on its pharmacokinetics. Given the low cost of fenbendazole, its high safety profile, accessibility, and unique anti-proliferative activities, fenbendazole would be the preferred benzimidazole compound to treat cancer. To ensure patient safety in the repurposing use of fenbendazole, it is crucial to perform clinical trials to assess its potential anticancer effects, optimal doses, therapeutic regimen, and tolerance profiles. This review focuses on the pharmacokinetics of orally administered fenbendazole and its promising anticancer biological activities, such as inhibiting glycolysis, down-regulating glucose uptake, inducing oxidative stress, and enhancing apoptosis in published experimental studies. Additionally, we evaluated the toxicity profile of fenbendazole and discussed possibilities for improving the bioavailability of the drug, enhancing its efficacy, and reducing potential toxicity.

Key Words:
Fenbendazolefenbendazole pharmacokineticscancer treatmentrepurposed drugsglycolysis inhibitorsreview
Fenbendazole, also known as methyl N-(6-phenylsulfanyl-1H-benzimidazole-2yl), is currently used as an antiparasitic therapeutic agent in dogs and other animals. In humans, other benzimidazoles, such as mebendazole and albendazole, are used as antiparasitic agents (1). Fenbendazole exerts its antiparasitic effects primarily in the anterior intestine by depolymerizing microtubules, inhibiting intestinal secretory vesicle transport. Fenbendazole binds to beta-tubulin in parasites, causing microtubule destabilization and hindering tubulin polymerization. This destabilization disrupts cellular function, such as glucose uptake, thereby affecting the energy management of parasites. Due to its poor absorption by oral administration, fenbendazole is particularly effective for targeting intestinal parasites (2).

In August 2016, fenbendazole garnered global attention as a potential anti-cancer therapy following the complete recovery success story of Joe Tippens, who was diagnosed with small-cell lung cancer. At the time, Tippens was undergoing a clinical trial for a novel anti-cancer drug. Meanwhile, under the guidance of a veterinarian, Tippens began self-administering 222 mg fenbendazole orally, along with vitamin E supplements, CBD oil, and bioavailable curcumin. After three months of self-administration, a PET scan revealed no detectable cancer cells in his body. Notably, Tippens was the only patient cured of cancer among the 1,100 clinical trial participants (3). While the Joe Tippens case is compelling, it remains an anecdotal report. It underscores the need for rigorous clinical trials to validate the efficacy and safety of fenbendazole as an anti-cancer therapy.

The anti-cancer activity of fenbendazole has been studied across many cell lines, demonstrating anti-tumor effects against multiple cancer types (Table I) (4-7). Additionally, fenbendazole has shown efficacy against 5-FU, paclitaxel, and docetaxel-resistant cancer cells (5, 8, 9). Compared to albendazole, fenbendazole was more effective against 5-FU-resistant colorectal cells, likely due to its intervention in glycolysis (5).

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Table I.
Studies of fenbendazole in vivo and in vitro cell lines.

Although fenbendazole exhibits promising anti-cancer effects, experimental studies indicated its poor water solubility has hindered its therapeutic performance. When administered orally, fenbendazole struggles to reach systemic circulation and, subsequently, the therapeutic levels necessary to impact tumors (10-12). Addressing pharmacokinetic limitations is crucial to repurposing fenbendazole for cancer treatment.

This review focuses on the pharmacokinetics of fenbendazole when administered orally and its promising anticancer biological activities, such as inhibiting glycolysis, down-regulating glucose uptake, inducing oxidative stress, and enhancing apoptosis. In addition, we evaluate the toxicity profile of fenbendazole and discuss possibilities for improving the bioavailability of the drug, enhancing its efficacy, and reducing potential toxicity. This comprehensive review aims to provide a detailed understanding of fenbendazole’s potential as a repurposed anti-cancer agent and outline the necessary steps for its clinical application.

Anti-cancer Mechanisms and Targets of Fenbendazole
Studies attribute the anti-cancer mechanisms of fenbendazole to increasing p53 activation, inhibiting the GLUT1 transporter and hexokinase, and reducing glucose uptake in cancer cells (4). Enhanced glycolysis is a crucial signal of tumor progression (13-15). Under anaerobic conditions, glycolysis produces lactate, which increases acidification in the tumor microenvironment and leads to drug resistance (16). Metabolic disturbances, such as glutamine overuse, further enhance glycolysis, creating a feedback loop for tumor growth (15, 17). Fenbendazole has been found to inhibit glucose uptake, resulting in reduced lactate levels (4). Thus, fenbendazole can serve as a viable treatment for drug-resistant cancer cells.

Fenbendazole exhibits several other mechanisms contributing to its anti-cancer effects, primarily by disrupting energy metabolism. It functions as a microtubule destabilizing agent, impairs proteasomal function, and inhibits glucose metabolism. Glucose, a primary energy source for tumor cells, is metabolized through aerobic glycolysis and delivered across the cell membrane via the GLUT1 transporter (18). Unlike normal cells, cancer cells perform glycolysis to metabolize glucose to lactate even under aerobic conditions (13, 16, 19). Although aerobic glycolysis is not an efficient method of supplying energy and appears to produce less ATP than oxidative phosphorylation, it provides essential materials for tumor cell growth, such as nucleotides, amino acids, and lipids (20, 21). Additionally, the ATP/ADP and NADH/NAD+ ratios in tumor cells remain high, indicating sufficient ATP supply through glycolytic tumor metabolism (22).

The GLUT1 transporter has been highly expressed in 99% of patients with squamous cell carcinoma and 50% of patients with adenocarcinoma (23-25), leading to being proposed as a promising therapeutic target in cancer therapy (26). Fenbendazole induces mitochondrial translocation of p53, indicating activation of the p53-p21 pathway, which inhibits GLUT transporter expression and prevents glucose uptake in cancer cells (4). Through p53 activation, fenbendazole is believed to impede hexokinase II (HKII) (4, 7), the first glycolytic pathway enzyme critical for cancer cell growth. However, another study did not observe inhibition of HKII activity at 1 and 10 μM fenbendazole (10). As a primary enzyme in glucose metabolism, the inhibition of HKII would prevent tumor development (4, 27, 28). Therefore, fenbendazole’s actions on HKII warrant further exploration. Thus, through targeting GLUT1, HKII, and glycolysis, fenbendazole can lead to cancer cell starvation and reverse drug resistance, aiding cancer treatment.

In addition to glycolysis inhibition, fenbendazole induces apoptosis in cancer cells (4-7). In colorectal cancer (CRC) cells, fenbendazole triggers apoptosis through mitochondrial injury and the caspase 3-PARP pathway. In wild-type CRC, fenbendazole activates p53-mediated apoptosis by increasing p53 expression. Additionally, it induces necrosis, autophagy, and ferroptosis. In 5-FU-resistant CRC, fenbendazole triggers apoptosis without affecting p53 expression, likely enhancing p53-independent ferroptosis-augmented apoptosis (5).

Fenbendazole also acts as a microtubule destabilizing agent. Microtubule-targeting agents are promising cancer treatments due to the microtubules’ roles in mitosis, cell structure maintenance, and other cellular events (29-33). Some cancer therapy drugs inhibit microtubule polymerization (vincristine, vinblastine), while others stabilize microtubules (paclitaxel, docetaxel), leading to apoptosis and metaphase arrest (34). Fenbendazole shows microtubule depolymerizing activity in human cancer cell lines and demonstrates anticancer effects in vitro and in vivo (4, 10, 35). Fenbendazole induces cell cycle arrest in the G2/M phase (4, 36) and demonstrates tubulin destabilization activity at concentrations of 1 and 10 μM, with more cell cycle arrest demonstrated at higher concentrations (10 μM) (10).

When administered orally at micromolar concentrations, fenbendazole induces cytotoxicity and effectively blocks cancer cell growth. Fenbendazole also causes oxidative stress and activates the MEK3/6-p38MAPK pathway, inhibiting cancer cell proliferation and enhancing apoptosis. Fenbendazole reduces toxicity to normal cells while maintaining its anti-cancer effects of impairing energy metabolism and restraining cancer cell migration and invasion (37). Beyond oncology, fenbendazole shows potential in treating pulmonary fibrosis by inhibiting the progression of bleomycin-induced lung fibrosis (36).

Pharmacokinetics of Fenbendazole
Given that fenbendazole has not been approved for regulatory use in humans, pharmacokinetic data for this drug is limited. While no clinical trials have tested fenbendazole in humans, insights can be drawn from in vitro and in vivo animal studies. The FDA recently granted a fast-track designation for developing oxfendazole, a major metabolite of fenbendazole, to treat human trichuriasis. Pharmacological studies of oxfendazole can help supplement the understanding of fenbendazole’s pharmacokinetics in humans.

Fenbendazole undergoes partial absorption in the liver, where it is rapidly metabolized by flavin-monooxygenase (FMO) and CYP3A4 enzymes to become its sulfoxide derivative, oxfendazole (fenbendazole sulfoxide) (38, 39). Additionally, CYP2J2 and CYP2C19 enzymes metabolize fenbendazole into hydroxyfenbendazole (40). Another metabolic pathway converts fenbendazole into fenbendazole sulfone (41, 42) by pre-systemic and systemic metabolism (43). Although fenbendazole sulfone predominates in the plasma following administration (41), oxfendazole is the primary metabolite responsible for the biological activity of fenbendazole (44). Through systemic metabolism (43), oxfendazole is reduced back to fenbendazole (44) rather than first-pass metabolism (Figure 1) (45).

Figure 1.
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Figure 1.
The metabolites of fenbendazole. Structures based on the metabolic scheme shown in the Fenbendazole UN FAO document (42).

In male rats, the maximum concentration of fenbendazole was observed to be 0.32 μg/ml (Table II) (10). After hepatic metabolism, fenbendazole and its metabolites are excreted via the feces and urine. A study performed in cattle found that 36% of orally administrated fenbendazole was recovered in the feces, with none in urine. When administered intravenously, over 50% of the fenbendazole dose was excreted as hydroxyfenbendazole (46).

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Table II.
Pharmacokinetic profile of fenbendazole when administered orally to male rats at a dose of 10 mg/kg. After the peak concentration, the drug concentration remained lower than 0.1 μg/ml (10).

Due to its low water solubility and permeability of 0.3 μg/ml (11), fenbendazole struggles to reach systemic circulation at levels sufficient to affect tumors. Its drug release rate is 5% within 15 min and 81% within an hour (12).

Safety and Toxicity
In animals, fenbendazole demonstrated a high safety margin and low toxicity. A safety profile study of fenbendazole administered to cattle found that fenbendazole was well-tolerated, even when administered at six times the prescribed dose and three times the recommended duration (47). In rodents, its lethal dose (LD50) exceeded 10 g/kg, which is 1,000 times the therapeutic level. Lifetime studies in rats indicated no maternal or reproductive toxicity and no carcinogenesis. However, morphologic changes in hepato-cellular hypertrophy and hyperplasia were observed (48).

Oxfendazole, a major metabolite of fenbendazole, is well tolerated in humans. A randomized, double-blind, placebo-controlled, phase I study conducted in 70 healthy participants evaluated multiple ascending oral doses of oxfendazole, from 0.5 to 60 mg/kg. The dose study found acceptable safety and tolerability profiles, even after 5 repeated daily doses of up to 15 mg/kg. This clinical trial also characterized the disposition of fenbendazole, describing the drug as a one-compartment model with formation rate-limited elimination (43).

Although studies of the pharmacokinetics of oxfendazole can give insight into the safety of fenbendazole, it should be noted that the solubility of oxfendazole is 44.12 μg/ml (49), demonstrating much higher pharmacokinetic exposure than the solubility of fenbendazole at 0.3 μg/ml (11), even after the same oral dose (50). Further clinical studies using fenbendazole are needed to accurately assess its safety, toxicity, and therapeutic dose in humans.

Increasing Fenbendazole Solubility and Absorption
A significant challenge in using fenbendazole is its low water solubility and bioavailability. Improving the water solubility is essential, as it would reduce the amount of drug needed to reach the same therapeutic effect. With this increase in solubility, fenbendazole can also meet the requirements for use as a systemic anticancer drug. Several studies have investigated various vehicles to overcome this low solubility limit (Table III).

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Table III.
Studies exploring various vehicles to improve the solubility of fenbendazole.

Among the discussed vehicles for increasing the bioavailability of oral fenbendazole, it would be worthwhile to focus on dimethyl sulfoxide (DMSO), Salicylic acid, and methyl-β-cyclodextrin. DMSO and DNTC (DMSO, NMP, Tween-80, and Cremophor mix in a 1:3:2:2 ratio) are highly promising solvents that warrant further exploration. DMSO inhibits several cytochrome P450 subtypes (2C9, 2C19, 2E1, and 3A4) in a concentration-dependent manner (51, 52). Since 2C19 and 3A4 are known CYP450 subtypes that metabolize fenbendazole, inhibiting these enzymes would allow fenbendazole to stay in circulation at higher concentrations for longer periods. Through this increase in bioavailability, fenbendazole can prolong its effects on cancer cells. Fen-DMSO and Fen-DNTC have also been found to be cytotoxic and induce apoptosis in paclitaxel-resistant cells (53). Due to their enhanced cytotoxicity, DMSO or DNTC formulations could be beneficial in treating drug-resistant cancer types.

Another method to improve the solubility of fenbendazole would be to complex it with methyl-β-cyclodextrin at a 1:1 ratio. When fenbendazole is complexed with methyl-β-cyclodextrin, the complex can significantly increase the drug’s water solubility to 20.21 mg/ml, which is 60,000 times better than the average solubility of fenbendazole. With this complex, fenbendazole can meet the water solubility requirements (5-10 mg/ml) and could be tested in future clinical trials as a potential anti-cancer drug. Additionally, methyl-β-cyclodextrin increases the drug release rate of fenbendazole to 75% in 15 min, compared to 5% for pure fenbendazole (11).

Salicylic acid would also be an excellent vehicle to improve the drug release rate of fenbendazole. Fenbendazole-salicylic acid performed exceptionally well, achieving a 100% drug release rate in under 1 hour and a 1.052 mg/ml solubility. This significant drug release rate improvement could offer immediate therapeutic action. The enhancement in solubility is suggested to be due to intermolecular interactions such as carboxylic-carboxylic or carboxylic-amino groups forming hydrogen bonds (12).

Fenbendazole as a Cancer Therapy in Humans
Despite the lack of regulatory approval and extensive clinical trials for fenbendazole as a cancer treatment in humans, some cancer patients have self-administered the drug, as documented in case studies. Table IV discusses four case reports where fenbendazole has led to a reduction in tumor size (54, 55) and two cases (56, 57) where patients experienced drug-related hepatic dysfunction (Table IV). In both cases, despite the hepatotoxicity, patients’ liver function recovered rapidly upon discontinuing fenbendazole.

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Table IV.
Summarized patient case reports on the self-administration of fenbendazole for cancer.

Due to its accessibility over the counter at a relatively low price, patients have turned to fenbendazole as an at-home treatment for cancer. As the published case reports observed, the most common self-administered regimen involves taking 1 gram of fenbendazole orally once daily for three consecutive days, followed by four days off treatment (54-57). However, the use of fenbendazole for cancer therapy in humans requires further pilot and extensive clinical trials to establish effective doses and regimens. Patients with compromised liver function, liver cirrhosis, or liver cancer should use fenbendazole with caution. Additionally, combining fenbendazole with glycolysis inhibitors and hepatoprotective pharmaceutical or nutraceutical agents can lead to synergic therapeutic activity while reducing potential liver toxicity.

Conclusion and Perspectives
Fenbendazole’s disruptive effects on energy metabolism are fascinating areas of study that could lead to significant advancements in cancer treatment. Various studies in cell lines and animals have demonstrated the efficacy of fenbendazole in inhibiting tumors and targeting drug-resistant cancer cells through glycolysis inhibition. By increasing p53 expression and impacting multiple cellular pathways that act on GLUT and HKII, fenbendazole down-regulates glucose uptake, causing cancer cell starvation and enhancing apoptosis. Through this mechanism, fenbendazole effectively eliminates cancer cells while exhibiting no or acceptable minimal toxicity to normal cells.

Improving the solubility of fenbendazole is crucial for enhancing its bioavailability and reducing the drug needed to reach therapeutic effects. Future studies could compare these vehicles and test various concentrations to optimize fenbendazole’s solubility and drug release. Additionally, combining fenbendazole with hepatoprotective pharmaceutical, nutraceutical, and glycolysis inhibitors can be a promising approach to improving the drug’s effectiveness while reducing its potential reversible liver toxicity.

With its high safety profile, affordability, and minimal side effects, fenbendazole stands out as a potential option for cancer therapy. Moreover, fenbendazole is easy to acquire and can be administered orally, offering a less invasive treatment that can increase patient adherence. Furthermore, by inhibiting glycolysis in cancer cells and preventing lactate buildup, fenbendazole surpasses albendazole and mebendazole in treating drug-resistant cells, making it the benzimidazole of choice for cancer therapy.

Despite numerous success stories using fenbendazole and the extensive research performed in vitro and in vivo, repurposing fenbendazole for cancer treatment remains non-suggested by conventional medical institutions and oncologists. Clinical trials should be funded and performed to promote the possible application of fenbendazole as an inexpensive, well-characterized, and widely available anticancer therapeutic in animals and humans.

Footnotes
Authors’ Contributions

JN: Conceptualization, Visualization, Writing – original draft, Writing – review & editing; TQN: Conceptualization, Writing – review & editing; BH: Prepared the references, Writing – review & editing; BXH: Conceptualization, Supervision, Writing – review & editing. All Authors read the manuscript before submission.

Conflicts of Interest

All Authors declare no conflicts of interest in writing and publishing the manuscript.

Funding

The manuscript writing and submission are author-initiated with no funding.

Received July 9, 2024.
Revision received July 15, 2024.
Accepted July 17, 2024.
Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

Joe Tippen Cancer Story-Recently Shared With Me-For Your Consideration
wbcgaruss
wbcgaruss Member Posts: 2,520 Member
June 2023 edited February 17 #1
Joe Tippen's personal story of battling cancer. He was given 3 months to live. His story is certainly different let's say but when your life is in the balance that changes things. I am just going to leave a link to his blog covering the whole story and my friends you can draw your own conclusions. It is a worthwhile read. It is a true story and Joe is still alive today.

Joe is a financial strategist and executive with over 30 years of experience. For the last 13 years, he was the CEO of Strategic Capital Group LLC and SCG Advisors LLC (Vero Beach, FL), an investment management firm he co-founded.

Joe Tippen Quote: "I am a big OSU fan and I bleed orange. To that end, I belong to an OSU message board where we get online and cuss/discuss OSU sports. Two days after coming home from being told I’ve got 0% chance to survive, I read a post on the OSU sports board that simply said “If you have cancer or know someone who does, give me a shout” I had known the author of that post (and his sons) for a very long time, so I picked up the phone and called him.



Link to Joes Blog, it tells the whole story--

The Blog – Get Busy Living
https://csn.cancer.org/home/leaving?allowTrusted=1&target=https%3A%2F%2Fmycancerstory.rocks%2Fthe-blog%2F
Attitude is Everything has always been my mantra. It seems that the more troublesome an event or challenge I’ve faced, my natural defense mechanism (that I attribute to my parents, siblings and friends) is to use positive thinking as the kick starter and humor as the mechanism to power through the adversity.


Link to Joe's All Posts Page, categories, and other success stories other than his.

All Posts – Get Busy Living
https://csn.cancer.org/home/leaving?allowTrusted=1&target=https%3A%2F%2Fmycancerstory.rocks%2Fcategory%2Fall-posts%2F
Attitude is Everything has always been my mantra. It seems that the more troublesome an event or challenge I’ve faced, my natural defense mechanism (that I attribute to my parents, siblings and friends) is to use positive thinking as the kick starter and humor as the mechanism to power through the adversity.


Wishing You The Best

Take Care, God Bless-Russ

Fenbendazole 



______

Deep Roots at Home
Joe Tippens -- Joe Tippins’s Fenbendazole Protocol For Cancer
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Joe Tippens Fenbendazole Protocol For Cancer
Cancer cells. Photo credit: samlevin on Visualhunt.com
The Fenbendazole Cancer Protocol has been gaining rapid interest over the past couple years. Now there are numerous fenbendazole cancer success stories.

The most famous story is of a man who was diagnosed with stage-4 small-cell Lung cancer and was sent home with a 3-month life expectancy. Joe Tippins started taking fenbendazole (Panacur C), a dog de-wormer, the 1 gram packages his veterinarian recommended, with some additional supplements. The following PET scan showed remarkable improvement, and after a few months, he was declared cancer-free.

Here is Joe’s fascinating story. (Refresh this article if the video is slow to appear).



Joseph Clark is yet another early documented story with end stage cancer that fenbendazole eradicated!

Joe Clark writes: “Saying ‘Fenbendazole without vitamins will have very little affect’ wasn’t true for me! I had stage 4 kidney cancer that had spread to my IVC, right atrium of my heart, both lungs, pancreas, hip and spine. In April of 2019, I was deemed terminally ill with six months to live. Last ditch treatment was immunotherapy. I was given 3 half doses and it was determined that I became highly toxic from the treatment which caused pancolitis. Treatment was terminated. The first week of August started taking Fenbendazole, NO vitamins, no CBD. Now second week of October, 2019, MRI scans at Stanford shows my largest tumor in my left kidney was GONE! All other tumors shrinking considerably! Now January, 2020, Stanford MRI scans show no evidence of disease!! (NED) all cancer gone! I’m still taking Fenbendazole 3 days on, four days off, consistently. No vitamins! STANFORD is now producing Fenbendazole in their lab for human study! I’m living proof of Fenbendazole treatment with no vitamins. It doesn’t mean they won’t help, but they aren’t needed to kill cancer cells. All my records are proof positive and can be reviewed.” ~Joe Clark (May, 2020)

Later, Joe updates: “I am still cancer-free as of Sept, 2021. See my published story provided by my Stanford Medical Center Team (Dr. Sandy Srinivas). I AM CASE #1 The 63 year old male. https://www.scitechnol.com/peer-review/fenbendazole-enhancing-antitumor-effect-a-case-series-2Kms.php?article_id=14307 I STILL TAKE FENBENDAZOLE 3 DAYS ON, 4 DAYS OFF, a 1gr pkg. This is extremely safe to take every day, no days off.  No elevated liver enzymes with this protocol. Save your life and don’t let your doctors frighten you that this will harm your liver, It’s just not true! God bless, and good luck.” ~Joe Clark

Here are even more stories (scroll down and click each image to open). Joe Tippin’s blog is My Cancer Story Rocks.

3 Main Mechanisms In Which Fenbendazole Kills Cancer
1) Apoptosis induction. Cancer cells are stopped from dividing by inhibiting cell division (mitosis) and…by inducing programmed cell death (apoptosis), all of which result in tumor eradication. (Source1, Source2)

2) Inhibition of glucose uptake in cancer cells. Malignant cells are known to have an enormous glucose uptake. Cancer cells normally consume glucose 200 times faster than ordinary cells. This can be seen in PET scans – the metabolically active sites, which use more radioactive glucose can be clearly seen. Fenbendazole limits cancer cell fueling with sugar by limiting the glucose uptake, while decreasing the amount of canals that take glucose into the cancer cells from the blood. (Source1, Source2)

3) Reactivation of the p53 gene. There is an increasing number of studies that confirm the fact that fenbendazole might truly increase the strongest tumor suppressor in our bodies – p53. (Source)

“[These] various modes of action mean that there is almost no possibility for cancer cells to develop resistance to the drug. Because it targets several routes, if resistance develops to one mechanism of action, fenbendazole can still affect cancer cells in other ways. Furthermore, fenbendazole may be used with other anticancer treatments owing to its unique mechanism of action and low toxicity.” (source)

**I also want to say, I would never encourage someone to do this without gathering more research and working with a functional doctor. 

The Current Joe Tippins Protocol 
The Joe Tippins Protocol relies mostly on substances that target cancer cells’ weak points. Specifically, cannabidiol (CBD) binds directly to voltage-depenent anion channels (VDAC), curcumin inhibits hexokinase-2 (HK2) and closes VDAC pores, and fenbendazole impairs HK2 by binding to it and through the interaction with the β-tubulin, resulting in cell cycle arrest and apoptosis in cancer cells (self-destruction). (source) The current Joe Tippins protocol no longer calls for the addition of Vitamin E.

Joe Tippins main treatment protocol for fenbendazole is relatively simple and easy. (source)

• 1 gram (1 packet) of Panacur C is advised to be taken seven days a week. It is recommended that it should be taken with a meal. The tested FenBen Lab product is option.

• Two – 600mg tablets of this Curcumin (turmeric) per day are recommended. This should be taken seven days a week. It also helps by increasing the p53 levels in the body.

• 25mg of CBD oil everyday. (Each dropper is graduated which allows for easy dosing). To be taken sublingually, under the tongue.

• Berberine helps in starving and weakening of the cancer cells so it is recommended to take it 2-3 x/d.

• Quercetin is recognized as an anti-inflammation agent, and it is recommended to be taken 1/day.

• Vitamin E (optional): 400-800mg per day, seven days a week.

THIS PAGE contains the original protocol; the modified stronger protocol; the protocol for preventing cancer relapse; and the prophylactic protocol for someone who was always cancer-free.

THIS PAGE lists numerous clinical studies favorable to fenbendazole (or mebendazole) and links to read them.

HealNavigator also has an almost identical protocol, and they offer several levels of consultations with medical staff.

For a FREE 30 minute consultation, go here. For a Fenbendazole consultation (at a reasonable $150) go here. (I am not an affiliate in any way). An integrative oncology nurse (RN) will personalize the fenbendazole protocol for your condition.

How Johns Hopkin’s Lab Discovered Fenbendazole Prevented Cancers. Why is Johns Hopkins not shouting this to the rooftops? (PS not surprisingly, the page has been taken down, but look at the page url and you’ll still see the words “2015/surprise_finding_yields_a_possible_tumor_fighting_drug”.)

What If Your Pet Has Cancer? 
This is such a helpful video. Dr. Jones also highlights the human implications. 5 minutes. (Refresh this article if the video is slow to appear).



“Beloved, I pray that in every way you may prosper and enjoy good health, as your soul also prospers.” ~3 John 1:2

***For the Full Spike Protein Protocol to protect from transmission from the “V” and to help those who took the “V”, go here.



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Medical Disclaimer: I am no longer a practicing medical professional, and I am not doctor. I am a mother. I do seek scientific confirmation of the safety and effectiveness of the herbs and remedies I use. Using remedies is a personal decision. Nothing I say on this blog is intended to treat or prevent disease. Consult your own doctor.
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Hi! I’m Jacqueline!
Thanks for being part of this journey with me.

Welcome to my own little place on the internet! Home is where I love to be. I feel there is no greater place to incubate souls. These days you’ll find me using my experiences here to write about herbal remedies and natural health research — a big passion of mine. But being a wife and mother is not easy. It is challenging and potentially lonely. I get that. I wanted to create a place to connect with and support other moms for creating a natural, healthy, and fulfilling home life.
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Comments
RachelMarch 23, 2023 at 7:14 pm
Do you have a recommended protocol for parasite cleansing using the FenBen capsules?

Reply
JacquelineMarch 23, 2023 at 9:39 pm
Hi, Rachel,
I do not personally have a protocol, but I can share this one: https://fenbendazolehelp.org/fenbendazole-dosage-guide
Please read it carefully and follow instructions to get your CMP (Comprehensive Metabolic Panel) as they suggest to monitor your liver and kidney function.
Blessings!
Jacque

Reply
JenApril 3, 2023 at 5:30 pm
Folks, please don’t do this without the support of someone who has. I had late stage cancer. I am doing well. My somatic mutation was the p53 gene. I will not take fenben or menben except as a last resort.

First of all, once you start, you can’t really come off. I have had friends who went on fenben and when they tried to ween themselves off due to side effects, their cancers came roaring back.

Second, fenben is still a drug. Long term use can create gut health issues, liver issues, etc. So make sure you have exhausted your NATURAL therapies first.

Finally, it isn’t a cure-all. I will be honest, I am not trying to be rude to you, Jacqueline, but it gets frustrating seeing posts like these. Inevitably, someone who has never fought late stage cancer will flippantly send it to someone like me and act as if we’re just too stupid or undisciplined to get healthy. I can’t tell you the number of people who have told me “Just take bitter apricot seeds,” or “Have you tried high dose vitamin C?”

Um, yup. I can guarantee I have done more research and tried more treatments than… well, just about anyone I know, really, including my oncologist. But many people mistakenly read something like this and just assume it applies to everyone. I personallythink it’sa way to compartmentalize and thinkt heybare protected or that things.wpuld be differfor them, but
it’s still annoying.

Sorry to get on my soapbox, but this is a huge pet peeve of mine. I think it’s disrespectful to those who legitimately put in the work to get healthy and still died. Maybe I am just still raw from losing yet another friend, but I am just so tired of people oversimplifying the complex nature of cancer.

I know countless amazing people who have died while taking fenben. The sad fact is that most late stage cancer patients die regardless of what treatment plan they choose. Natural, integrative, or conventional- there aren’t high survival rates.

It is heartbreaking wondering why you were spared and friends weren’t- wondering if it is going to come back all the time.

So, yeah, fenben is a great tool to have in the toolbox, but it isn’t perfect.

Reply
JacquelineApril 5, 2023 at 12:57 am
Hi, Jen,
I am sorry for the losses you have suffered.
Did you by any chance read the post and see where I give a medical disclaimer and also encourage people to get more research and work with a functional doctor if they do it?

Reply
Cris DorvalJune 21, 2023 at 9:28 pm
Jen I am so sorry about the battle you’ve been fighting, and the friends you’ve lost along the way. I’m so glad you are an advocate in the trenches.

Although I’ve never had cancer, I’ve had multiple life threatening occurances of autoimmune disease and then a combo of tickborne illnesses that caused pericardial effusion with cardiomegaly. Being sick stinks in and of itself but you are right the lack of understanding, lack of compassion and oversimplification can grate on your last nerve. After a year of high fevers, anemia, heart problems, vasculitis and overall unwellness, I went to worship in my faith community and heard on the way out the door “do you go in the sun? the sun will cure you”. (she said this to me while I was sporting my summer tan) It was hard not to get angry. It was insulting. My response was “no, no….If sun was the cure for what I am dealing with I wouldn’t be dealing with it” and left it at that. Was I annoyed? more than I should’ve been. This is one of many insensitivities and I’m telling you simply to affirm you and let you know I truly understand.

Because my health issues have been complicated and often off the beaten path, I’ve tried many “off label” or unconventional treatments. When I went to the liver doctor in Boston after 8 years of treatment for stage 4 liver damage due to autoimmune hepatitis, this is what I was told ” We don’t get many happy endings around here, but you are clearly in remission!” They marveled at me. They celebrated! And they knew I had tried natural and unconventional treatments. It worked for me.

If it wasn’t for brave people posting articles like this, like Jacque and others, I would not have been able to research for healing. I’ve pulled together catalogs full of ideas that I’ve researched, tried, kept or discarded. I also am a praying woman, and when I hit a wall with my health, I take it to God asking for His leading, help and healing. It’s amazing what I’ve stumbled upon, seemingly randomly, shortly after pleading with God for wisdom and guidance. There is just so much out there to know. We are so limited.

So without this amazing resource (and many many others) I just would not have had access to these new ideas and concepts. The time I’ve had to personally invest in my health would never have been available to me through main stream doctors, and the cost of paying these professionals for their time, limited as it is, would be astronomical.

I see Jacque’s website as one of the greatest blessings on the internet. The difference between what she posts and well meaning people coming up to us pushing their ideas on us through ignorance is that 1) Jacque is a trained medical professional. 2) What she shares she researches extensively and often tries on her own first. 3) She is laying things out for us to sort through and glean, not pressing it on anyone. And finally, 4) she is a godly woman who has zero agenda except to help others by sharing what she knows. She does this in faith and in love for humanity and God.

Jen, I just want to say again how sorry I am you’ve gone through such hardship, and how much I understand your pain and frustration. Just know that this website is one of the good ones.

May God bring healing and peace to your grieving soul.

Cris

Reply
Stephanie RMay 7, 2023 at 8:07 am
Is fenbendazole safe to take while nursing? I’m still breastfeeding my 19 month old, mainly just during the night now, but am wondering if I need to wean her before I begin taking it.

Reply
JacquelineMay 7, 2023 at 8:26 pm
Hi, Stephanie,
Since I am not a doctor I would defer to the doctor you choose to tailor a plan for you.
In my post, I wrote this: “**I also want to say, I would never encourage someone to do this without gathering more research and working with a functional doctor.”
My hunch is that fenbendazole is a no while nursing or breastfeeding just out of an abundance of caution for your baby, but please check with your trusted physician.
I am praying for you now,
Sending peace, Jacque

Reply
Cris DorvalJune 20, 2023 at 8:40 am
I watched the Joe Tippins interview, and found it interesting when the interviewer at the end said some people didn’t like this potential cure to give cancer patients “false hope”. Hope is powerful in and of itself! Sometimes what we tell our bodies is what happens. How we think matters! But more than this, why not try everything? I’m so grateful for these discoveries! There is always hope.

Reply
JacquelineJune 20, 2023 at 9:59 pm
Yes, Cris,
If I thought hope was unimportant, I would never write this blog.
I believe one of the greatest gifts God has given us is hope. After all, that is what his promises are designed to do – inspire hope.
It gives us the ability to look at any situation and know that regardless of how it may appear God is going to come through. This is the essence of what hope is.
Hugs to you, friend!
~Jacque

Reply
GregMarch 19, 2025 at 10:31 pm
When I click on the link for the Fenbendazole product, it takes me to an Amazon page where I can buy the yellow box for $9.99, but then your website says that an adult should take 222 mg/”one capsule” three times per week as part of the cancer prevention protocol or 5 days in a row for parasite removal. I’m just wondering if the yellow box product contains 222 mg. capsules? – i.e., is 222 mg. equal to one gram, since the yellow box seems to contain 1 gram capsules? If the yellow box is the one to buy, how many boxes would need to be purchased to get you through one, 5-day treatment cycle? Thank you!

Reply
JacquelineMarch 19, 2025 at 11:27 pm
HI, Greg,
I am trying to put out the success stories of others without actually recommending something specifically. I am just reposting their testimonies and since I’m not a doctor (I am an RN), I don’t recommend but I know these repurposed drugs ARE curing cancer in many, not all.
As written in the post, “Joe Tippins started taking fenbendazole (Panacur C), a dog de-wormer, the 1 gram packages his veterinarian recommended, with some additional supplements.”
Similarly, in the same post, Joe Clark updates: “I am still cancer-free as of Sept, 2021. See my published story provided by my Stanford Medical Center Team (Dr. Sandy Srinivas). I AM CASE #1 The 63 year old male. https://www.scitechnol.com/peer-review/fenbendazole-enhancing-antitumor-effect-a-case-series-2Kms.php?article_id=14307 I STILL TAKE FENBENDAZOLE 3 DAYS ON, 4 DAYS OFF, a 1gr pkg. This is extremely safe to take every day, no days off. No elevated liver enzymes with this protocol.
If you enlarge and read the front of the Panacur C package, it says there are 3 packets which contain Fenbendazole granules at 222mg/gm
So that is one way to do it…

Other patients of Dr. Makis’s use 222mg fenben tablets all they way up to 1000mg. Here are some posts to read that give many different ways to consider in light of YOUR specific needs:
https://deeprootsathome.com/fenbendazole-q-a-important-things-to-know-useful-tips/

This post contains 4 Fenbendazole Protocol Options & Product Source: https://deeprootsathome.com/fenbendazole-studies-doctors-dosage-for-aggressive-cancers/

In this post: https://deeprootsathome.com/ivermectin-fenbendazole-for-tumors-ibd-alzheimers-stories/ you will find this story:
8. “A friend of mine R. has been taking Fenbendazole since April. The oncologist only gave R. 6 months to live after his prostate cancer diagnosis. The doctors wanted to remove the cancer, but R. heard from a fishing friend about Fenbendazole, so he told his oncologist that he wanted to wait 6 months before opting for any surgery or chemo. R. proceeded to take Fenbendazole and 6 months later he was completely cancer free. R. still takes Fenbendazole every day as a precaution. He takes 450mg per day. R.’s cancer marker started out at 1900, and is now at 41. After starting Fenbendazole, the number continued to decline. R. has talked to people with stage 4 pancreatic cancer that are also cancer free thanks to Fenbendazole. All of these cancer survivors continue to take Fenben daily.”

And there are more clear cut testimonies on various stage 4 cancers in this post: https://deeprootsathome.com/case-studies-of-patients-who-cured-their-own-stage-4-cancers/

I hope that helps,
Jacque

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__________
Clinical Oncology: Case Reports

Case Report, Clin Oncol Case Rep Vol: 4 Issue: 2

Fenbendazole Enhancing Anti-Tumor Effect: A Case Series
Ryan S Chiang1*, Ali B Syed2, Jonathan L Wright3, Bruce Montgomery3 and Sandy Srinivas4

1Department of Medicine, Stanford University Medical Center, Stanford, CA, United States

2Department of Radiology, Stanford University Medical Center, Stanford, CA, United States

3Departments of Urology and Medicine, University of Washington, Seattle, WA, United States

4Division of Medical Oncology, Department of Medicine, Stanford University MedicalCenter, Stanford, CA, United States

*Corresponding Author:
Ryan Chiang
Department of Medicine
Stanford University Medical Center Stanford
410 Station Park Circle Unit 107
San Mateo CA 94402, CA, USA
E-mail: sandrysri@stanford.edu

Received: October 27, 2020 Accepted: January 15, 2021 Published: February 10, 2021

Citation:Chiang RS, Syed AB, Wright JL, Montgomery B, Srinivas S (2021) Fenbendazole Enhancing Anti-Tumor Effect: A Case Series. Clin Oncol Case Rep 4:2


Abstract
Abstract

Background: Fenbendazole (FBZ) is a cheap and readily available anti-parasitic commonly used in veterinary medicine. FBZ belongs to the benzimidazole drug class which destabilize microtubules through a mechanism similar to the anti-oncogenic vinca alkaloids. Although there are no reported cases in the literature, there have been several anecdotal stories published on website blogs with individuals praising its ability to treat a wide variety of cancers.

Case Presentations: Herein we describe the cases of three patients with various genitourinary malignancies who demonstrated complete response after receiving FBZ therapy as a single or supplementary chemotherapeutic agent. In two patient scenarios, they had experienced progression of metastatic disease despite multiple lines of therapy prior to initiation of FBZ. No side effects from FBZ were reported.

Conclusion: FBZ appears to be a potentially safe and effective antineoplastic agent that can be repurposed for human use in treating genitourinary malignancies. Further research is necessary to define the role of FBZ as a chemotherapeutic option.

Keywords: Fenbendazole; Veterinary medication; Anti-parasitic; Medication repurposing; Immunotherapy; Genitourinary malignancy; Renal cell carcinoma; Urothelial carcinoma
Keywords
Fenbendazole; Veterinary medication; Anti-parasitic; Medication repurposing; Immunotherapy; Genitourinary malignancy; Renal cell carcinoma; Urothelial carcinoma

Introduction
There has been growing popularity in recent years for the use of Fenbendazole (FBZ) as a single agent or supplementary therapeutic to chemotherapy for those suffering with various forms of cancer. FBZ is a cheap anti-helminthic medication commonly used in veterinary practice and readily available in pet stores and off commercial websites. However, despite multiple anecdotal stories and news outlet reports for its efficacy in treating metastatic cancer, the clinical literature behind utilizing FBZ as a potential anti-neoplastic agent remains nonexistent. Existing scientific studies have primarily studied its mechanism of action through the use of animal models [1-3]. Herein, we describe three cases where patients achieved complete responses, including two who experienced progression after multiple lines of therapy, when FBZ was used alone or in combination with standard therapies.

Case Presentation
Case 1

A 63-year-old Caucasian male presented with flank pain, rapid weight loss, and transient fever. Abdominal Computed Topography (CT) revealed a 3 cm left lower-pole solid renal mass. He underwent open partial nephrectomy with pathology showing pT1a highgrade clear cell Renal Cell Carcinoma (RCC). Several months later, he developed persistent left flank pain with finding of a 5.2 cm left kidney mass. Fine Needle Aspiration (FNA) biopsy redemonstrated clear cell RCC, and pazopanib 800 mg was initiated. Follow-up CT revealed a new 1.4 cm pancreatic head/body lesion, persistent left renal mass, and signs of sigmoid colitis. Given the concerns for disease progression and intolerable side effects, pazopanib was discontinued and cabozantinib was initiated. Interval Magnetic Resonance Imaging (MRI) showed stable size of recurrent left renal mass, mild decrease in 2.9 cm pancreatic head lesion, stable 1.2 cm distal pancreatic body lesion, and new 1.1 cm right posterior iliac bone lesion. Cabozantinib was ultimately discontinued due to persistent intolerable side effects. One month after discontinuation, repeat MRI showed increase in size of recurrent left renal mass, mild decrease in 2.3 cm pancreatic head lesion, stable 1.4 cm distal pancreatic body lesion, and unchanged 1.1 cm right posterior iliac bone lesion. Third-line treatment with nivolumab was initiated, and he only received three total treatments (240 mg × 3) over the course of a month due to developing severe rash and colitis. He was treated with steroids with resolution of colitis. During this time, he also started alternative therapy with FBZ 1 gm three times per week at the suggestion of one of his friends with head/neck cancer. Interval MRI imaging found near complete resolution of the previously noted left renal mass as well as decrease in pancreatic head/body and right posterior iliac spine lesions (Figure 1). Serial imaging for the past 10 months have not shown any evidence of recurrence or metastatic disease. He has continued taking FBZ without any reported side effects.

clinical-oncology-renal-mass
Figure 1: Near complete resolution of persistent left renal mass (left image) after initiation of three total doses of nivolumab and FBZ therapy 1 gm three times weekly for several months (right image).

Case 2

A 72-year-old caucasian male presented with increasing lower urinary tract symptoms and a urethral lesion. He underwent distal penectomy with pathology showing pT2 high-grade urothelial carcinoma of the urethra with focal squamous differentiation. Four years later, the patient developed a cough with finding of a 5.5 cm × 4.0 cm left hilar mass and a 1.5 cm × 1.4 cm left upper lobe nodule, with multiple abnormal AP window lymph nodes, the largest measuring 1.8 cm × 0.9 cm all avid on PET CT. Brain MRI revealed a right occipital lobe metastasis. Bronchoscopy with biopsy revealed squamous carcinoma. His presentation was felt most consistent with a lung primary and the patient was treated with gamma knife radiotherapy and carboplatin, paclitaxel, and pembrolizumab. Subsequent sequencing of the lesion from the penectomy and bronchoscopy demonstrated shared PIK3CA, RB1, CCND1 and CDKN2A alterations demonstrating that the pulmonary disease represented metastasis from urethral primary. The patient developed progressive retroperitoneal disease while on pembrolizumab maintenance and was treated with gemcitabine and cisplatin for 6 cycles over the course of 4 months with near complete response. However, interval CT imaging demonstrated increase of an aortocaval node from 1.2 cm × 1.0 cm on to 1.5 cm × 1.5 cm. No therapy was initiated and a subsequent scan demonstrated further increase to 2.0 cm × 1.5 cm with no evidence of progression elsewhere (Figure 2). The patient opted for complementary therapy with FBZ 1 gram orally three days per week, vitamin E 800 mg daily, curcumin 600 mg daily and CBD oil while awaiting more substantial disease progression before initiating additional systemic therapy. Serial CTs from the past 9 months showed progressive decrease in size to 0.5 cm × 0.5 cm, complete radiographic response.

clinical-oncology-radiographic-response
Figure 2: Near complete radiographic response of a 2.0 cm × 1.5 cm aortocaval node (left image) after initiation of alternative therapy including FBZ therapy 1 gm three times weekly (right image).

Case 3

A 63-year-old Caucasian female presented with increasing lower urinary tract symptoms and hematuria. CT imaging revealed a 7.5 cm right lateral bladder mass with extension to the right pelvic sidewall and right-sided hydronephrosis requiring percutaneous nephrostomy. There was no evidence of metastatic disease, consistent with clinical T4 tumor. Transurethral Resection of Bladder Tumor (TURBT) demonstrated a large necrotic mass with pathology confirming urothelial carcinoma with 85% squamous and 2% sarcomatoid histology. She was treated with Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (AMVAC) for 6 cycles over the course of 4 months along with concurrent FBZ 1 gram three times weekly. Follow-up CT revealed no evidence of disease with minimal residual thickening in the right inferior bladder wall (Figure 3). She declined to proceed with cystectomy and remains on surveillance with no evidence of progression.

clinical-oncology-bladder-mass
Figure 3: Resolution of 7.5 cm right lateral bladder mass (left image) after treatment with TURBT, Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (AMVAC), and concurrent FBZ 1 gm three times weekly (right image).

Discussion
In summary, we have three patients with different primary genitourinary tumors who demonstrated complete response after receiving FBZ therapy. This raises the question of how effective FBZ can be as an anti-oncogenic agent and merits further investigation. To our knowledge, there has not been a similar case series reported.

FBZ belongs to a class of microtubule-destabilizing agents known collectively as the benzimidazoles. The ability to disrupt microtubule polymerization to induce mitotic arrest and promote apoptosis is a feature shared with the vinca alkaloids. Proposed mechanisms for FBZ’s anti-tumor properties include inhibition of proteasomal activity, p53 activation, cytotoxicity via tubulin disruption, and downregulation of glycolytic enzymes crucial for cancer cell survival [1,4]. Other benzimidazoles such as albendazole possess anti-tumor properties through influencing the HIF-1-alpha pathway which is critical for VEGF expression and certain aspects of glycolysis [5]. The variety of mechanisms by which this class of medications functions may help limit the propagation of resistant cancer cell lines through targeting multiple avenues of cancer cell survival.

FBZ has been safely utilized as an anti-parasitic for various different animal species and could be repurposed for treating human malignancies. Several benzimidazoles have already shown promise for human repurposing. One example is parbendazole, which has demonstrated potential efficacy as a supplementary therapy to gemcitabine in patients with pancreatic cancer [6]. Mebendazole has been shown in case reports to be efficacious with few side effects in patients with metastatic adrenocortical carcinoma and metastatic colon cancer [7,8]. Mebendazole and flubendazole have also been shown to be effective in animal studies for glioblastoma multiforme and hematologic malignancies, respectively [9,10]. Given evidence of high tolerability and applicability to a wide range of malignancies, this warrants further investigation for FBZ and other benzimidazoles as safe chemotherapeutic options.

Prior studies have demonstrated cancer response to immune checkpoint inhibitors such as nivolumab as a third-line agent in mRCC [11]. The duration of therapy was often much longer requiring a median therapy duration of 6 months with 24% overall response rate in third-line treatment. It is possible that our first patient with mRCC would have achieved a significant response to nivolumab alone without FBZ. However, given the complete radiologic response on only 1 month of immune checkpoint inhibitor therapy, it also seems likely that FBZ played a notable role in inducing remission. This is supported by the fact that our patient has remained in extended remission while only on FBZ for nearly a year without further administration of immune checkpoint inhibitor therapy.

Conclusion
There remains limited data with few published studies on the anti-oncogenic properties of FBZ. Other benzimidazoles have been studied to a larger extent, and the knowledge can be drawn upon to help guide future FBZ studies and to gauge the efficacy of this drug class whether as a solitary agent or in combination therapy. Given the potential benefits of FBZ with what seems to be a limited toxicity profile, further research is warranted to evaluate the clinical settings in which this medication may be beneficial and repurposed for patients with progressive genitourinary malignancy and possibly in other malignant settings as well.

References
Dogra N, Kumar A, Mukhopadhyay T (2018) Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways.Sci Rep 8: 11926.
Gao P, Dang CV, Watson J (2008) Unexpected antitumorigenic effect of fenbendazole when combined with supplementary vitamins.J Am Assoc Lab Anim Sci 47: 37-40.
Duan Q, Liu Y, Rockwell S (2013) Fenbendazole as a potential anticancer drug.Anticancer Res 33: 355-362.
Dogra N, Mukhopadhyay T (2012) Impairment of the ubiquitin-proteasome pathway by methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate leads to a potent cytotoxic effect in tumor cells: A novel antiproliferative agent with a potential therapeutic implication.J Biol Chem 287: 30625-30640.
Zhou F, Du J, Wang J (2017) Albendazole inhibits HIF-1α-dependent glycolysis and VEGF expression in non-small cell lung cancer cells.Mol Cell Biochem 428: 171-178.
Florio R, Veschi S, di Giacomo V, Pagotto S, Carradori S, et al (2019) The benzimidazole-based anthelmintic parbendazole: A repurposed drug candidate that synergizes with gemcitabine in pancreatic cancer.Cancers (Basel) 11: 2042.
Dobrosotskaya IY, Hammer GD, Schteingart DE, Maturen KE, Worden FP (2011) Mebendazole monotherapy and long-term disease control in metastatic adrenocortical carcinoma.Endocr Pract 17: e59-e62.
Nygren P, Larsson R (2014) Drug repositioning from bench to bedside: Tumour remission by the antihelmintic drug mebendazole in refractory metastatic colon cancer.Acta Oncol 53: 427-428.
Bai RY, Staedtke V, Aprhys CM, Gallia GL, Riggins GJ (2011) Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme.Neuro Oncol 13: 974-982.
Spagnuolo PA, Hu J, Hurren R, Xiaoming W, Gronda M, et al. (2010) The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma.Blood 115: 4824-4833.
Yip SM, Wells C, Moreira R, Wong A, Srinivas S, et al. (2018) Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the international metastatic renal cell carcinoma database consortium.Cancer 124: 3677-3683.