The Big Bad Wolf of Treatment Related Toxicities

Mar 21, 2024

Who’s afraid of the Big Bad Wolf?

Literally, everyone, especially when the Big Bad Wolf symbolizes treatment-related toxicities.

Two of the most feared treatment related toxicities are severe oral mucositis (SOM) during the treatment of head and neck cancer (HNC) with chemoradiotherapy and severe autoimmune disease from checkpoint inhibitors.

SOM is so fearsome because of the intense pain involved, which interferes with speaking, swallowing, and eating. 70% of patients require hospitalization for pain relief, tube feeding, and IV hydration and antibiotics. These patients may also require temporary or permanent discontinuation of effective anticancer treatment, which predisposes to disease recurrence. The only approved agent against SOM is a growth factor called palifermin, but its approval is limited to the stem cell transplantation setting.

While severe checkpoint-inhibitor-related side effects (irAEs) occur much less commonly and predictably than SOM, their potential to cause irreversible organ damage and death is not to be underestimated. It is common to treat irAEs with corticosteroids and sometimes immunosuppressants, but their use may compromise the anticancer efficacy of checkpoint inhibitors and predispose to infections.

Like the more resilient materials that the third Little Pig used – i.e., bricks – current evidence from late-stage clinical trials suggests that treatment with the EpicentRx lead therapies, RRx-001 (nibrozetone) and AdAPT-001, may fortify patients to withstand all the huffing and puffing from several treatment-related toxicities including SOM and severe irAEs without the side effects of corticosteroids or other immunosuppressants.

A lot of preclinical work was required to work out the specific mechanisms by which RRx-001 (nibrozetone) and AdAPT-001 protect normal tissues from injury but suffice to say that no pigs, little or otherwise, were involved – or harmed.