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    Experimental oral drug may be effective in treating metastatic basal cell carcinoma

    Dr. Marmur
    New York — A new experimental oral medication is proving highly effective in the treatment of metastatic basal cell carcinoma (BCC), according to a recent study.

    Treatment modalities for advanced BCC cases typically include surgery and/or radiation, but these approaches often are insufficient. Vismodegib (GDC-0449, Genentech) is an experimental oral inhibitor of the Sonic hedgehog signaling pathway, which is known to play an important role in the development of the disease.

    "Contrary to popular belief, basal cell carcinoma can metastasize, and when it does, the outcome can not only be very disfiguring but also deadly,." says Ellen S. Marmur, M.D., associate professor and chief of the division of dermatologic & cosmetic surgery at the Mount Sinai Medical Center in New York. "Patients with advanced metastatic BCC have often tried surgery but this approach is not always successful, depending on the stage and/or location of the growing tumor. Therefore, other treatment options such as vismodegib are direly needed for patients with advanced or metastatic BCC."

    Phase 2 trial

    Dr. Marmur was a co-investigator in a recent phase 2 trial that evaluated the efficacy and safety of vismodegib in patients with advanced BCC. The international, single-arm, multicenter, two-cohort, open-label study enrolled 104 patients with advanced BCC, including 71 patients with locally advanced BCC (laBCC) and 33 with metastatic BCC (mBCC). The laBCC patient cohort had BCC lesions that were considered either inoperable or for whom surgery would result in substantial deformity and for which radiotherapy was unsuccessful or contraindicated. Study participants received 150 mg vismodegib orally, once daily until disease progression or intolerable toxicity.

    Results showed a 43 percent and 30 percent overall response rate in locally advanced BCC (laBCC) and metastatic BCC (mBCC), respectively, as assessed by an independent review. Study investigators assessed the overall response rate for laBCC and mBCC at 60 percent and 46 percent, respectively. The median duration of progression-free survival (PFS) by independent review for both metastatic and locally advanced BCC patients was 9.5 months. Results also showed that vismodegib could shrink tumors or heal visible lesions, or prevent them from growing any further in 75 percent of patients.

    "I was extremely impressed with the ability of this medication to melt away these BCCs. Though the trials are still underway, the efficacy of vismodegib is substantial and very promising for this patient population, especially for those patients who may not have any other good treatment option," Dr. Marmur says.

    Adverse events

    The most common drug-related adverse events seen in study patients ranged from muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhea. Serious adverse events were observed in 25 percent of patients (26 patients), of which 4 percent (four patients) were considered to be related to vismodegib, including cholestasis, syncope, cardiac failure and pulmonary embolism. Fatal events were reported in seven patients (7 percent); however, none were considered by investigators to be related to the drug and were thought to be associated with patients' standing comorbidities.

    "The adverse events may be considered acceptable to patients in light of the risks of severe disfigurement resulting from tumor growth and surgical removal or even death. In many patients, these BCCs are ulcerated and so extensive that the chance of having the tumor melt away and heal is a significant advance and a great improvement in quality of life. Many of these patients have few options, and this drug may represent their best therapeutic option," Dr. Marmur says.

    According to Dr. Marmur, surgery is still considered the gold standard therapy for patients with advanced BCC. In those patients where surgery is not an option, radiation therapy can be tried, but hard data is still lacking with regard to the true efficacy of radiation in advanced and/or metastatic BCC. A combination of surgery and radiation therapy can be attempted, particularly in those patients where the cancer involves the main nerve trunks and surgery cannot clear the whole tumor.

    Protocol pending

    Many outstanding questions in terms of an ideal protocol still remain, Dr. Marmur says, and just how long a patient may have to take the medication to remain disease-free after the cancer has apparently cleared is still unknown. Ideally, patients who become disease-free could begin to take a lower dose or an intermittent maintenance dose of vismodegib to keep potential recurrences at bay, but such a protocol would take years to establish.

    "When an aggressive basal cell carcinoma tumor metastasizes, we cannot do very much for the patient outside of palliative surgical and/or radiation treatment approaches. For this study, we were surprised how quickly we enrolled patients with advanced disease, which led us to believe that metastatic BCC is more common than we thought. This underscores the dire need for an effective medication to become available to this patient population suffering from this very debilitating and lethal tumor," Dr. Marmur says.

    Disclosures: Dr. Marmur reports no relevant financial interests.

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