PodMed starts out this week with Rick quipping, "what does stopping hedgehogs have to do with curing cancer?" Turns out the most common type of skin cancer- basal cell carcinoma- may have finally met its match with a drug that inhibits a pathway known as 'hedgehog,' two studies in the New England Journal of Medicine demonstrate.
The drug is known by the awkward name of 'vismodegib,' and it was used in two different patient populations: those who had locally advanced or metastatic disease, and folks with basal cell nevus syndrome, where they develop hundreds or even thousands of basal cell carcinomas during their lifetime. At best, people with this syndrome must undergo repeated surgical procedures, resulting in scarring and discomfort. Those with locally advanced or metastatic disease face death from basal cell carcinoma.
The study looking at locally advanced and metastatic disease enrolled 33 patients with metastatic disease and 63 patients with locally advanced disease. Both groups received 150mg of oral vismodegib daily. The response rate among those with metastatic disease was 30%, while 43% of those with locally advanced disease responded. The study on basal cell nevus syndrome treated 41 patients, who received the same dose of vismodegib as the previous study, planned for 18 months or until intolerable side effects developed. This interim analysis revealed that the drug reduced both the number of basal cell nevi in the treated group compared with the placebo group, and reduced the size of the lesions.
Great news, right? Yes, but side effects were common in both studies. In the study on those with basal cell nevus syndrome, over 50% discontinued the drug due to side effects, including muscle cramps, hair loss, taste disturbance, weight loss and fatigue. In the study on those with locally advanced or metastatic disease, 7 deaths due to adverse drug reactions were noted. Seems like targeting this pathway is a great idea but further drug development to refine the target and reduce such side effects is clearly desirable.
As I opine in the YouTube this week, maybe we should all take a lesson from this pathway's namesake, 'hedgehog,' and become nocturnal, as is the animal. Failing that, a very large number of these basal cell cancers could be avoided by avoidance behavior: staying out of the sun, using hats and clothing to cover up, and use of sunscreen. Regular all body skin examination could also catch them early, before locally advanced or metastatic disease develops. In this case we do know that early treatment is likely to be successful. For those unfortunate folks with basal cell nevus syndrome, seems that for now, regular check ups and excisions remains the best strategy, and we know additional hedgehog inhibitors will be developed, hopefully with a more benign side effect profile.
Other topics this week include two studies on the disturbing rise in multidrug resistant tuberculosis and a new agent for treating it in NEJM, screening for intimate partner violence in Annals of Internal Medicine, and the bleeding risk associated with aspirin for primary prevention of heart disease in JAMA. Until next week, y'all live well.