Hedgehog Inhibitor Alternative Dosing Advantageous for BCC

Posted on the 08 April 2021 by Thiruvenkatam Chinnagounder @tipsclear

Many experts in the treatment of locally advanced or metastatic basal cell carcinoma (BCC) have adopted alternative off-label dosing regimens for oral hedgehog inhibitors in a successful effort to maintain efficacy while reducing treatment discontinuation. caused by unacceptable side effects, Vishal Patel, MD, told Innovations in Dermatology: Virtual Spring Conference 2021.

"It is the tolerability issues that make these drugs very difficult to prescribe and use regularly. What we have seen in recent years is that many alternative dosage regimens have been published which have been both effective in treating the tumor and keeping the tumor clear and at bay while lowering the side effect profile " explained Patel, a Mohs surgeon and director of the skin oncology program at the George Washington University Cancer Center in Washington, DC.

Product labeling for the two available hedgehog pathway inhibitors, vismodegib (Erivedge) and sonidegib (Odomzo), requires once daily treatment until disease progression or unacceptable toxicity. Studies show that, when used in this way, these agents achieve objective response rates in the order of 40% for patients with locally advanced CBC and 15-33% for those with metastatic CBC.

"The bottom line in these patients is not that the drugs work - although they can work quite remarkably - but rather that almost all patients experience at least one side effect. And grade 3 or 4 side effects that can lead to drug discontinuation occur in about 25% of patients, "he told the MedscapeLIVE sponsored conference! and the producers of the Hawaii Dermatology Seminar and the Caribbean Dermatology Symposium.

The classic side effects of hedgehog pathway inhibitors are muscle spasms, hair loss, fatigue, loss of taste, diarrhea, and weight loss.

Among the alternative dosing regimens that have been published with good results, mainly in retrospective single-center case series, there is a weekday / weekend strategy at the Cleveland Clinic and an Italian approach involving an initial treatment of 3 to 4 months a day. followed by a switch to therapy every other day.

But Patel is in favor of a different off-label diet instead of the Food and Drug Administration's recommended daily dosage indefinitely. It takes advantage of the fact that most patients don't start to experience classic side effects until around 3 months.

"What we started to recommend as a much better option for patients who have to take the drug potentially forever is that the drug be dosed daily for 3 months to shrink the tumor and achieve optimal effect, then at that. then we reduce the dose to every other day, then every third day, or even up to a week as long as the tumor continues to stay at bay. If there is any sign of recurrence or if a screening biopsy shows a tumor, we reinstate the medication daily, "says the dermatologist.

This strategy requires careful monitoring for the appearance of typical side effects. In addition, an important caveat about sonidegib is that it should not be co-administered with drugs that are moderate or strong inhibitors of CYP3A, so it is essential to have a complete medical history when taking it. administration of this drug, Patel noted.

Patel did not disclose any relevant financial relationship. MedscapeLIVE! and this news organization is owned by the same parent company. This article originally appeared on, which is part of the Medscape Professional Network.

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