Treatments: Best Practices
Treatments vary depending on the stage of cancer progression. Below is a brief overview of each stage of skin cancer1, followed by widely accepted treatments.
● Stage 0: abnormal cells appear on the epidermis.
● Stage 1: tumors are no more than a millimeter thick. Ulceration can occur.
● Stage 2: tumor becomes 14mm thick with varying degrees of ulceration.
● Stage 3: cancer has spread (metastasized) to one or more lymph nodes. Other tumors can be found no more than 2 cm away from the point of origin.
● Stage 4: cancer has metastasized to other parts of the body such as the brain, lungs, bone, or GI tract, far from point of origin.
Basal Cell Carcinoma (BCC)
BCC is the most common form of skin cancer. It rarely ever metastasizes, but should be dealt with as quickly as possible. Current treatment options (which are explained in more detail below) include excision surgeries (Mohs is most common), photodynamic therapy (PDT), radiation therapy, and topical medicine. Of these options, excision generally has the best cure rate, but if disfiguration is a possibility, topical cream or PDT might be better options. In very rare cases of metastasis, the recently FDA approved drug called vismodegib. It is sold under the name Erivedge and works by preventing expression of a gene present in 90% of BCC cases. It is advised not to take this drug if pregnant or wanting to become pregnant as it can cause birth defects.
Squamous Cell Carcinoma (SCC)
SCC is similar to BCC in that it almost always curable when caught in an early stage. When it is allowed to grow, it can cause disfigurement and even death when it metastasizes (although only 210% of cases do). The treatment options are the same as the ones for BCC listed above. Treatment should be chosen based stage of progression and with cosmetic effects in mind.
Mohs Micrographic Surgery
This surgery has been accepted as the most effective method of removing basal cell, squamous cell carcinoma, and melanoma in the early stages (0,1, and 2). The surgery is done by a physician under local anesthesia. The tumor is removed using a scalpel, using a very small free margin (amount of healthy tissue removed with tumor). After the cancer is removed, it is frozen and sectioned into thin slices. The slices are stained and examined for cancerous cells in the margins. If cancer is still present, the process is repeated until all cancer is removed. The advantage to this surgery is the small free margin and an astounding cure rate of 98%. This type of surgery was not used in the past for melanoma, but advances in specific stains for melanocytes have made it a very viable option.
Lymph Node Dissection
This form of surgery is used when the cancer has spread from the skin to nearby lymph nodes (stage 3 or 4), where it can enter the lymphatic system and be spread throughout the body. The surgeon will examine the lymph nodes nearest to the cancer to see if it has migrated. If they have, the surgeon will remove the lymph nodes to keep the cancer localized. This will allow for a more targeted treatment and increase the curability of the cancer.
Radiation is not usually used to treat the initial melanoma, but it is commonly given after excision or lymph node surgery to decrease the likelihood that the cancer will come back.. An external source of high energy radiation is directed very precisely to the affected areas, killing the cancer cells. Radiation can also be used to relieve symptoms caused by the spread of the cancer to other organs. Typical side effects include sunburned appearance of the skin, hair loss, fatigue, nausea, and vomiting.
Chemotherapy should only be used for advanced melanomas, particularly when they have metastasized. This type of treatment uses drugs injected into the veins or taken orally to attack cancerous cells throughout the body. It may not be as effective for melanoma as it is for other cancers, but it can still be a viable option. There are many chemo drugs including: dacarbazine, temozolomide, paclitaxel, carmustine, cisplatin, carboplatin, and vinblastine. Chemo drugs can sometimes be more effective when combined with interferon alpha or interleukin2. This type of therapy is called chemoimmunotherapy. Depending on the drug and dose, typical chemo side effects can occur.
Photodynamic Therapy (PDT)
PDT uses drugs called photosensitizing agents along with light and oxygen to kill cancer cells. The drugs are delivered via injection or applied to the skin depending where the cancer is. Since the cancer lacks the same structure as healthy cells, the photosensitizing agent preferentially gets absorbed by the abnormal cells.9 A specific wavelength of light is applied to the area to activate these agents. When exposed to tissue oxygen, the reaction creates singlet oxygen which is extremely cytotoxic and kills off the cells. This treatment has many advantages including precise targeting of cancer cells, being minimally invasive and safe, little or no scarring, cost effective,and can be repeated. Commonly used photosensitizing agents include Photofrin, Levulan, and Metvixia.
This drug is a monoclonal antibody developed by BristolMyersSquibb. It acts by binding to cytotoxic Tlymphocyte antigen 4 (CTLA4) receptors to block certain ligands and activate cytotoxic Tcells. Although its complete mechanism is still unclear, it is believed that antitumor effects from ipilimumab are due to these augmented Tcell immune responses. Cytotoxic Tlymphocytes are able to recognize and destroy cancer cells. The drug was approved for use in March 2011 and is sold under the name Yervoy.
This drug is a topical cream that is used as an alternative to surgery when it can be disfiguring. It has been used for squamous cell carcinoma, melanoma, and actinic keratoses(premalignant skin that appears scaly). It is important to stress that this cream is not a cure, but rather a means of stopping cancer cell growth and killing abnormal cells. There are two concentrations available under the name Zyclara.
Interleukin 2 (IL2)
This drug is marketed under the named Proleukin. It is a naturally occurring cytokine signaling molecule for the immune system. It functions biologically by stimulating lymphocyte production (T cells, B cells, and Natural Killer cells), enhancing lymphocyte toxicity, and stimulating the long term growth of IL2 dependent cells. These are important because it can rally the bodies immune system to fight off cancer cells. Proleukin is administered through IV in 15 minutes every 8 hours for 5 days at a hospital. The patient is given 10 days off, then the regime is repeated again. IL2 is incredibly dose sensitive, so low doses are usually given to avert side effects, especially if other treatments are being prescribed in adjunct.
Surgical techniques are rather advanced, so research is moving toward immunotherapy, vaccination and therapeutic drugs.
The investigational drug lambrolizumab was designated as a Breakthrough Drug by the FDA on April 24, 2013. This is significant since this designation allows for expedited development and review of the drug. The FDA sees a lot of potential from previous clinical data, so it will likely make it to market much sooner than if it had not been designated a Breakthrough Drug. lambrolizumab is an antibody developed by Merck, that disrupts the PD1 (programmed cell death protein 1) pathway. Essentially, melanoma cells can evade the body’s immune system by making it believe the cancer cells are normal and healthy. Treatment with lambrolizumab will allow the immune system to take over and fight off the cancer. As of August 2013, clinical trials have shown significant antitumor behavior. Researchers are very pleased with the rate of responses and the duration of those responses.
BristolMyersSquibb is currently recruiting for a phase I study of BCG (Bacillus Calmette Guerin) vaccine for patients with advanced metastatic melanoma. The trial is combining the BCG vaccine with ipilimumab.17 BCG is a vaccine originally developed for tuberculosis, but is known to potentiate immune responses. This response is not specifically targeted at melanoma cells, however when injected into tumors it has been shown to be beneficial to stage 3 patients. BCG will most likely act as an adjuvant when taken with ipilimumab. This trial will investigate the efficacy and safety of this combination therapy. Efficacy is the main end point measure since BCG is known to be safe. The study is estimated to be completed in June of 2016.
POL103A is a vaccine entering phase III trials developed by a company called Polynoma LLC. The vaccine is a melanoma antigen vaccine immunotherapy, used in patients that have stage 2 or 3 melanoma that have already undergone surgery.19 Its aim is to prevent relapse of the cancer. In phase I and II trials, Polynoma has been able to prove the safety of POL103A. The trial which is estimated to conclude in July 2016, has enrolled about 1,060 patients over 35 centers. POL103A is a novel vaccine treatment that shows a lot of promise.
Talimogene Laherparepvec (TVEC)
TVEC is an oncolytic, genetically engineered virus being developed by Amgen. The virus functions by secreting the cytokine GMCSF, which is involved in initiating the immune response and also by directly killing cancer cells. Its phase III study completed in March of 2013 and showed positive results, particularly in the durable response rate (DRR). These results, when compared to the results from competing immunotherapies such as ipilimumab, are actually better. The goal is to elicit a response that can last continuously for six months. TVEC is still awaiting FDA approval, however business analysts and investors predict that if TVEC is approved, it could not only compete with ipilimumab, but would be more profitable.
Centers of Excellence
● University of Texas MD Anderson Cancer Center this center is widely respected by themelanoma community for their expertise in all of the surgeries, biochemotherapy, UV light and radiation therapies.
● Memorial Sloan Kettering Cancer Center have an elite team of surgeons and specialists and also highly recommended by the skin cancer community.
● Dana Farber Cancer Institute (Boston, MA) experts in treatment, prevention and clinical trials.
● California Pacific Medical Center – Center for Melanoma Research and Treatment some of the most renowned specialists in the nation.
● Kimmel Cancer Center at Jefferson University Hospitals recognized by Melanoma Hope Network as being a center of excellence.