New Drug Shows Significant Results In Rare Skin Cancer Treatment
June 7, 2012

New Drug Shows Significant Results In Rare Skin Cancer Treatment

Doctors charged with treating patients with a rare form of one of the most common types of cancer in the US may have a new weapon for their fight after a clinical study has shown a particular drug has proven very effective in both the treatment and prevention of the disease.

The new drug, vismodegib (or Erivedge), has been found to dramatically shrink basal cell carcinoma (BCC) skin cancers and prevent the formation of new ones in patients with basal cell nevus syndrome (BCNS), or Gorlin Syndrome -- a rare genetic condition that causes anywhere from dozens to thousands of skin cancers to from on a patient´s body. The primary treatment for this condition has been surgical removal.

Results of this new study, published in the New England Journal of Medicine, are significant and hint at the possibility of a new alternative treatment for BCNS. However, scientists note that side effects are usually a drawback to the use of oral medication.

The phase II clinical study was led by researchers at New York-Presbyterian Hospital/Columbia University Medical Center (NYPH/CUMC) and Children´s Hospital of Oakland Research Institute (CHORI), and included researchers from Stanford University School of Medicine.

The research comes five months after vismodegib became the first drug in its class to gain FDA approval. The drug targets a molecular signaling pathway in cells called the Hedgehog signaling pathway. It works by inhibiting the pathway, which is inappropriately activated in basal cell carcinomas. While the pathway is important in early embryonic development, it is generally inactive in healthy adults.

The study is the first to evaluate the drug in patients with BCNS. Jean Tang, MD, PhD, assistant professor of dermatology at Stanford, and colleagues randomized 42 patients to receive either vismodegib or a placebo for a maximum of 18 months. Overall, the study tracked more than 2,000 existing surgically eligible basal cell skin cancers (SEBs) and documented 694 new SEBs, on the patients.

The patients receiving vismodegib experienced and average of 2.3 new SEBs, compared with 29 for the placebo group over the course of the trial. For those taking the drug, the diameter of clinically significant skin cancers decreased an average of 65 percent, compared with only 11 percent among the control group.

Surprisingly, the trial was stopped early because of the overwhelming effectiveness of the drug, and it was then considered unethical not to offer the drug to those participants in the placebo control group.

“In many patients, we observed a dramatic reduction in the size of the lesions within one to two months,” said study coauthor David R. Bickers, MD, the Carl Truman Nelson Professor and chairman of dermatology at CUMC.

“How often in your life do you get to have worked within a field where you finally get to test a drug that actually changes people´s lives?” said study leader Tang. “We were very excited about the results.”

“In most subjects, all the carcinomas clinically disappeared. No tumors progressed while the subjects took vismodegib,” she noted.

BCNS, a generally non-lethal form of skin cancer, affects about 1 in 50,000 people and often strikes during childhood. The constant growth of BCC tumors have been primarily treated by surgical removal, but persistent operations leave scarring, and over time, some BCC tumors can become inoperable.

“These patients usually have severe scarring by the time they reach adulthood,” Tang said. “The cancer generally doesn´t kill you, but obviously it affects the quality of life. Many patients never marry, never have families, they face more limited job opportunities. There currently are no good treatment options.”

Tang cautioned that, while vismodegib may be an effective replacement for surgical removal, it does not permanently cure patients, as the tumors returned once the treatment stopped. The drug, however, did slow down the process. The drug also has some side effects that include loss of taste, muscle cramping, hair loss and weight loss.

Still, earlier clinical trials found vismodegib to be an effective treatment for BCNS, and based on the positive results from the trials, the FDA approved on January 30, 2012 the use of vismodegib for adults with BCNS who cannot be treated through surgery or radiation.

“Vismodegib is a new treatment option for those with extensive disease, particularly those whose lives may be devastated by the disease and the need for repeated treatment,” Bickers said. However he would not recommend vismodegib for all BCNS patients, especially since the side effects have been found to occur in at least half the patients taking the drug, many of whom opted to discontinue treatment.

About 2.8 million people are diagnosed with BCC in the US every year. The disease, mainly caused by increased exposure to the Sun, is generally not life threatening. However, the tumors can invade nearby tissues and become disfiguring and even spread elsewhere in the body. While rarely fatal, it can be quite painful and lead to other complications.

“The purpose of the study was to see whether, by using this targeted molecular therapy, we could match the performance of a surgeon, and in many ways, we could,” said Bickers. “The challenge now is to see if we can lessen the adverse effects while achieving the same therapeutic benefits -- by modifying the dosing schedule or perhaps by alternating drug treatment with other modalities such as photodynamic therapy, which can be effective for smaller lesions.”

“It is a landmark day for patients with basal cell carcinoma and all those involved in their care -- the greatest advance in therapy yet seen for this disease,” wrote John Lear, MD, (Manchester Royal Infirmary and the Dermatology Centre of Hope Hospital in Manchester, UK) in an accompanying editorial.

Vismodegib treatments cost $7,500 per month, with most treatments lasting about 10 months.