Archive for category Skin Cancer

New Treatments for Advanced and Metastatic Melanoma

By Mai Brooks

Melanoma, the deadly skin cancer, is on the rise. In the United States in 2010, there were estimated 68,130 new cases of invasive cancer and 46,770 of in situ melanoma. In the same year, 8,700 people were predicted to die from this malignancy. Melanoma is curable if it is detected early and can be surgically removed. When melanoma has spread to lymph node(s) or when it is more than 4 mm thick, there is a chance of metastasis (spread to distant organs). Melanoma could spread to the following organs: lung, liver, brain, bone, intestine, pancreas, adrenal, kidney, spleen, heart, and thyroid. Imaging tests such as Pet CT and brain MRI may be done to look for metastasis. Most patients with metastatic melanoma die within one year. The 2-year survival rate is only 10-20%. Current treatments include chemotherapy, of which dacarbazine is the most commonly used. Over the past decades, many drugs and vaccines have been tested, with no success. The last drug approved was interleukin-2 in 1998, but it is so toxic that physicians rarely use it nowadays. Neither it nor the other approved drug, dacarbazine, has clearly demonstrated improved survival. This year, two new drugs are being introduced. The first drug is Yervoy (ipilimumab), which was approved by the FDA in March 2011. The second agent is vemurafenib; it has finished its clinical trial and awaits approval.

Yervoy is an antibody that blocks T-lymphocyte associated antigen 4 (CTLA-4). This blockage increases T-cell proliferation, which results in a more active immune system to attack the melanoma cells. A recent clinical trial enrolled 502 patients with previously untreated metastatic melanoma. The patients were randomly assigned to either dacarbazine chemotherapy plus Yervoy, or chemotherapy alone. Overall survival was significantly longer in the group receiving Yervoy plus dacarbazine than in the group receiving dacarbazine (11.2 months versus 9.1 months). At one year, 47% of the Yervoy patients are alive, in comparison with 36% in the chemotherapy only group. At two years, 29% of the Yervoy patients are alive, in comparison with 18% in the chemotherapy only group. At three years, 21% of the Yervoy patients are alive, in comparison with 12% in the chemotherapy only group. Yervoy can result in severe immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated side effects may involve any organ system. The most common severe adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. Yervoy costs $120,000 for a complete course of treatment, which consists of four infusions given over a three-month period.

The second promising new drug, vemurafenib, targets a mutation in the gene BRAF (Serine/threonine-protein kinase B-Raf). About 50% of melanoma cases have this mutation. The clinical trial enrolled 675 patients with previously untreated, metastatic melanoma with the BRAF mutation. Patients were randomly assigned to receive either vemurafenib or dacarbazine. At six months, overall survival was 84% in the vemurafenib group and 64% in the chemotherapy group. Common adverse events associated with vemurafenib were joint pain, rash, fatigue, hair loss, squamous-cell carcinoma, photosensitivity, nausea, and diarrhea. In the study, 38% of patients required dose modification because of toxic effects. This drug is being considered for future potential approval by the FDA in melanoma patients. The price tag is unknown at this point.

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Skin Cancer and Alternative to Mohs Surgery

By Leonard A. Farber, M.D.

It is estimated that over 1 million new cases occur annually. It has also been estimated that nearly half of all Americans who live to age 65 will develop skin cancer at least once. The two most common forms of skin cancer are basal cell carcinoma and squamous cell carcinoma. They account for approximately 96% of all diagnosed skin cancers. Together, these two are also referred to as nonmelanoma skin cancer.

Basal cell carcinoma is the most common form of skin cancer and accounts for more than 90% of all skin cancer in the U.S. These cancers almost never spread (metastasize) to other parts of the body. They can, however, cause damage by growing and invading surrounding tissue. Squamous cell carcinoma is cancer that begins in the squamous cells, which are thin, flat cells that look like fish scales under the microscope. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Thus, squamous cell carcinomas can actually arise in any of these tissues. Squamous cell carcinoma of the skin occurs roughly one-quarter as often as basal cell carcinoma.

A surgical method that is often used to treat nonmelanoma skin cancer is called Mohs surgery. This highly specialized surgical technique involves first removing the visible tumor and then successive layers of skin one at a time until microscopic examination no longer reveals cancer cells. This surgery is performed while the patient is under local anesthesia. Removing and examining each layer takes about one hour, with much of this time spent looking at the removed skin. When done, the surgical wound is treated as needed. The treatment can include closing the wound with stitches, covering the surgical site with skin from another area of the body (skin graft), and moving healthy skin from a nearby area to cover the surgical wound (skin flap).

But, Mohs surgery is not the only way to successfully treat skin cancers? Surgery on the nose, ears, eyelids or lips may cause disfigurement or require reconstructive surgery under a general anesthetic to maintain the natural appearance. Brachytherapy with the Flexitron system is an effective alternative treatment for BCC (Basel Cell Carcinoma) and SCC (Squamous Cell Carcinoma) skin cancer and avoids the need for reconstructive surgery. It also has its advantages over surgery for patients with a large number of lesions, elderly patients, or patients who are otherwise inoperable, and advantages over external beam radiotherapy as it requires shorter treatment times and less side effects.

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