Fenbendazole is a broad-spectrum antiparasitic drug used in both humans and animals. It has a long track record of use, particularly in animals (where it is used to treat Ascaris, hookworm and trichomoniasis), but only limited experience with its single dose activity against human parasites. It has also been found to be effective in experimental settings against some cancer cells. It is a potential candidate for combination therapy with chemotherapy and radiation as an immunosuppressant, enhancing the efficacy of both drugs by decreasing tumor cell sensitivity to them.
It is also known to inhibit proliferation in cancer cells, and enhance the effectiveness of radiotherapy and chemotherapeutic agents by increasing tumor permeability. This effect is due to a decrease in protein synthesis, and has been found to be independent of p53 status.
Moreover, fenbendazole is reported to reduce the uptake of glucose by cancer cells and to increase their sensitivity to glucose inhibition. This has been attributed to the formation of an inactive isoform of pyruvate dehydrogenase, which can block the uptake of oxidized glucose and prevent cellular energy production.
Our group has previously examined the effect of fenbendazole in the context of solid tumors using EMT6 mammary carcinoma cells in culture and in mice as well as 5-fluorouracil-resistant SNU-C5/5-FUR cancer cells, an established model for colorectal cancer. The results shown in Table 2 indicate that fenbendazole in maximally-intensive regimens significantly decreased the growth of EMT6 tumors in mice, and did not alter the radiation response to these tumors. The results of the other experiments shown in Table 2 confirm that fenbendazole has no impact on the growth of unirradiated tumors or on the time to four-fold tumor volume in irradiated tumors.
Febendazole alone is cytotoxic to EMT6 cells in vitro, and its toxicity increases with incubation time and under conditions of severe hypoxia. However, fenbendazole when combined with radiation or docetaxel in the dose-response experiments shown in Table 2 had no impact on the shape of either the radiation or docetaxel dose-response curves; the two drugs produced additive cytotoxicity.
In a recent case report (18) of a patient who was treated with pembrolizumab and fenbendazole, the authors described the development of liver injury as a treatment-related adverse event. Initially, this was thought to be related to an immune-related adverse event but it later became apparent that the patient had begun taking oral fenbendazole at the time of starting pembrolizumab treatment because of information she had found on social media sites regarding its anti-cancer effects. The patient subsequently regained her health and was able to resume receiving her scheduled pembrolizumab treatments, without additional liver damage. This case highlights the need to monitor for this type of adverse event in patients treated with novel anti-cancer agents and to evaluate if complementary therapies are safe and feasible. The author wishes to thank the Department of Medicine and the Division of Clinical Pharmacology, MD Anderson Cancer Center, for their assistance with this article. fenbendazole for humans cancer