Fenbendazole is an anthelmintic drug used to treat parasitic worm infections, and it has been shown to have antitumorigenic effects when combined with supplementary vitamins. Fenbendazole is a benzimidazole drug used to treat a variety of intestinal parasites, including pinworms and roundworms. The drug works by inhibiting the function of tubulin, which is necessary for maintaining the structure of cells and microtubules.
Fenbendazole Papers And Clinical Trials
There are currently no clinical trials investigating the efficacy of fenbendazole as a potential cancer treatment; however, several studies have investigated its possible antitumorigenic effects when combined with supplementary vitamins. These studies have yielded promising results and suggest that fenbendazole may help treat certain types of cancer. Source
Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent
This is an extensive list of fenbendazole papers, a drug used for worms and tapeworms. It is an effective anti-cancer agent, and it is being repurposed as an anti-cancer agent. Source It works by inhibiting the production of DNA in cancer cells, leading to their death. It has shown promise in several types of cancer, including brain cancers, ovarian cancers, and pancreatic cancers.
Mebendazole has been tested in several clinical trials for treating cancer, including Hodgkin lymphoma and testicular germ cell tumors. Mebendazole has also been used as a monotherapy or combination therapy for other cancers, including breast cancer, lung cancer, prostate cancer, cervical carcinoma, neuroblastoma, and non-Hodgkin’s lymphoma.
Toxicity
Fenbendazole is considered relatively safe in humans, and the most common side effects are gastrointestinal disturbances, nausea, and vomiting. As with other benzimidazoles, fenbendazole may cause photosensitivity reactions and skin depigmentation. There is evidence that fenbendazole may cause bone marrow suppression, and Fenbendazole has adverse effects on bone marrow cells in mice. If you experience these symptoms, it is best to stop taking them immediately.
Pharmacokinetics
The pharmacokinetics of mebendazole has been investigated in several studies in humans. Source Oral administration results in the absorption of mebendazole from the gastrointestinal tract. The plasma concentration of mebendazole rapidly increases to an initial peak after approximately 1–2 hours and then declines with a half-life of roughly 45 hours.
The drug is metabolized mainly by hydrolysis to benzimidazole carboxylic acid and sulfoxide metabolite; only small amounts are found unchanged in feces and urine. The sulfoxide metabolite has little or no antiparasitic activity, while the benzimidazole carboxylic acid has significant antiparasitic activity against some protozoan parasites.
Dosage: (100 mg chewable tablets)
The recommended dose for treating intestinal helminthic infections is 100 mg/day for 3 days. The drug is well tolerated at 100 mg/day doses, and the most common adverse effects are gastrointestinal disturbances and headaches. There have been no reports of pancreatitis or hepatic dysfunction in humans using fenbendazole papers at recommended doses.
Pre-clinical evidence in cancer—in vitro and in vivo
Mebendazole has shown activity against several types of human tumors. In particular, it seems to be effective against human melanoma cells, but not normal melanocytes. Mebendazole inhibits cell proliferation in vitro by inducing apoptosis and cell cycle arrest. In vivo, mebendazole inhibits tumor growth in xenograft models of glioblastoma multiforme (GBM), lung adenocarcinoma, prostate cancer, colon adenocarcinoma, gastric carcinoma, and pancreatic carcinoma. Mebendazole inhibits NF-kappaB activity and induces apoptosis through the caspase pathway. It also induces necrosis through the intrinsic mitochondrial pathway.
Human data in cancer
Mebendazole effectively treats anemia in patients with chronic myeloid leukemia (CML). It also improves neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). In CML, these symptoms are caused by the overproduction of white blood cells by cancerous bone marrow cells. In a recent study, researchers found that mebendazole significantly improved symptoms and quality of life in patients with CML receiving imatinib treatment (Gleevec). The mechanism behind how mebendazole works are not fully understood. It may inhibit angiogenesis, which is the formation of new blood vessels from pre-existing ones.
Clinical trials
Currently, there are two clinical trials of MBZ in cancer; all are for brain tumors. This article discusses the use of MBZ in oncology and the evidence for its anti-cancer properties. Source We also highlight several pivotal clinical trials that have been performed in this area.
Phase I
This is a clinical trial designed to evaluate the safety and efficacy of mebendazole in patients with advanced solid tumors. The primary objective is to determine the maximum tolerated dose (MTD) of mebendazole administered orally twice daily for three to four weeks combined with gemcitabine chemotherapy. Secondary objectives include evaluating the pharmacokinetic profile of mebendazole and its effects on inflammation, immune function, and apoptosis. The study is conducted at John Hopkins Hospital.
The molecule was repurposed from its original use as an antihelminthic agent for treating parasitic infections to novel cancer therapy. This repurposing was based on the observation that the drug targets tubulin-dependent pathways and inhibit tumor growth in animal models, including genetically engineered mice and humans with colon cancer. Mebendazole has been evaluated in phase 1 clinical trials for cancer treatment. In one study, mebendazole was safe at doses up to 50 mg/kg/day when administered orally for 28 days. Treatment with mebendazole resulted in dose-dependent decreases in serum lactate dehydrogenase (LDH) levels and histological changes consistent with cell death in patients with advanced non-small-cell lung cancer (NSCLC).
Phase I and II pilot study of MBZ
Another trial takes place at Cohen Children’s Medical Centre of New York. Source This will help us understand how MBZ works with other drugs to treat low-grade gliomas in children. We’ll learn whether MBZ helps extend the effect of current therapies. This is a phase I and II study, meaning this drug has not been tested on humans before or used to treat pediatric patients with low-grade glioma. The study will last 70 weeks. We’ll be comparing two groups of children with low-grade glioma: one group receiving standard of care treatment with anti-cancer drugs plus MBZ, and another group receiving standard of care treatment. In this study, half of the participants will receive a placebo, a tablet that looks and tastes exactly like the MBZ tablet but contains no active ingredient to make them better or worse. All participants will be given the same treatment twice a day over 70 weeks.
This trial determines if the standard dose of MBZ 100 mg twice daily is ‘well-tolerated’ and could improve patient outcomes when combined with the current three-drug regimen. Phase I of the study is an exploratory phase; individuals will be offered the chance to receive for 70 weeks the three-drug regimen + MBZ or else to enroll as part of the control group receiving the three-drug regimen alone. Phase II will determine overall survival.