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 The leading web portal for pharmacy resources, news, education and careers March 27, 2017
Pharmacy Choice - Melanoma Disease State Management - March 27, 2017

Melanoma Disease State Management

Skin Cancer: Focus on Metastatic Melanoma
by Darrell Hulisz, RPh, PharmD
Associate Professor, Department of Family Medicine, Case Western Reserve University, School of Medicine


In the United States, skin cancer is the most common form of malignancy, and is diagnosed in ~1 million Americans each year. There are various types of skin cancer, such as basal cell (BC) and squamous cell (SC) carcinoma. Malignant melanoma (MM) is clearly the most feared and deadly form of skin cancer. Although melanoma accounts for only 5-6% of skin cancer diagnoses, it accounts for 75% of the mortality due to skin cancer.

All forms of skin cancer are associated with overexposure to ultraviolet (UV) light, mostly from excessive sunlight. The incidence of skin cancer is increasing, but is still considered to be one of the most preventable types of cancer. Squamous cell carcinoma is more likely to become metastatic than BC, but only about 3-4% of cases that metastasize.

Melanoma differs from BCC and SCC since the malignancy actually develops within melanocytes, the cells that produce melanin. The National Cancer Institute estimates that over 68,000 new cases of melanoma will be diagnosed this year in the U.S. and cause 8700 deaths. In America the percentage of people who develop melanoma has more than doubled in the past 30 years.

The main risk factors for developing skin cancer include a history of chronic solar exposure, severe sunburn and intense intermittent exposure to the sun at an early age. Patients who have skin lesions considered to be pre-malignant, such as actinic keratoses and dysplastic nevi are also at risk. Other risk factors include lighter skin color, family or personal history of skin cancer, skin that burns, freckles or reddens easily in the sun. Less established risk factors include having blue or green eyes, blond or red hair, certain types and a large number of moles.

The main skin cancer preventive strategy is to reduce UV radiation exposure, especially in those at risk. All individuals should adopt effective sun protection habits, such as wearing sunscreen, hats, shirts, and sunglasses. Pharmacists should counsel patients on proper use of sunscreens and encourage patients to limit or abstain from using indoor tanning equipment. Patients with moles or skin lesions that have changed, relative to their original size, shape or color should be referred for medical evaluation. A simple ABCDE mnemonic has been used to aid in the early detection of malignant melanoma: Asymmetric moles, Border irregularity, Color variation, Diameter > 6mm, Evolving moles.

The initial treatment of melanoma is surgical excision of the suspected lesion(s). The lesion itself and often surrounding tissues and lymph nodes are then biopsied to determine the stage of disease. Optimal therapy for melanoma varies with the stage of disease. Surgical treatment alone may be acceptable for Stage I disease. Stage II or III melanoma are more likely to represent metastatic disease. Thus, these patients may receive interferon alpha with or without chemotherapy. Dacarbazine is the only FDA-approved chemotherapeutic agent used for advanced melanoma and is considered the first-line therapy. Unfortunately, the response rates are only 8-20% and survival time is less than eight months for Stage IV melanoma. Common adverse reactions associated with dacarbazine include bone marrow suppression (minor), phlebitis, nausea, and vomiting. It is one of the better-tolerated antineoplastic drugs. Other drugs used off-label for advanced melanoma are less effective than dacarbazine and include temozolomide, cisplatin, carboplatin, carmustine and lomustine. In general chemotherapy for advanced melanoma induces partial remissions in 10-20% of patients; however remission is usually short-lived and these drugs have not been shown to prolong survival. Occasionally, interleukin-2 and/or interferon alpha is used in combination with dacarbazine or other chemotherapy agent. Radiation therapy is usually reserved for treatment of melanoma with distant organ metastasis, such as brain or bone.

A novel and promising approach to treating advanced melanoma is immunotherapy. Ipilimumab is a human IgG monoclonal antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4). CTLA-4 is a molecule on T-cells that appears to regulate endogenous natural immune mechanisms. Ipilimumab blocks the activity of CTLA-4, thereby sustaining an active immune response on malignant cells. Results from a recent clinical trial were presented at the American Society of Clinical Oncology, Jun 2010 and published electronically by the New England Journal of Medicine. In this study, 676 patients with Stage III or IV melanoma were randomized to receive either ipilimumab plus a glycoprotein peptide100 vaccine (gp100), or ipilimumab alone, or gp100 alone. The median survival was 10 months in patients receiving ipilimumab plus gp100, versus 6.4 months with gp100 alone. The improvement in survival with the monoclonal antibody was both statistically and clinically significant. The compound is currently awaiting FDA approval and is marketed by Bristol Myers Squibb.

Given the prognosis of malignant melanoma and the lack of effective therapy for advanced disease, it is important for pharmacists to encourage patients to avoid sunburns, limit chronic solar exposure, properly use sunscreens, and refer patients for medical attention for atypical moles or other lesions that may look suspicious.

References:
  1. Glanz K, Yaroch AL, Dancel M, Saraiya M, Crane LA, Buller DB, Manne, S, O'Riordan DL, Heckman CJ, Hay J, Robinson JK. Measures of sun exposure and sun protection practices for behavioral and epidemiologic research. Arch Dermatol 2008;Feb;144(2):217-22.
  2. U.S. Preventive Services Task Force. Screening for skin cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;Feb 3;150(3):188-93.
  3. Lazovich D, Stryker JE, Mayer JA, Hillhouse J, Dennis LK, Pichon L, Pagoto S, Heckman C, Olson A, Cokkinides V, Thompson K. Measuring nonsolar tanning behavior: indoor and sunless tanning. Arch Dermatol 2008;Feb;144(2):225-30.
  4. Stulberg DL, Crandell B, Fawcett RS. Diagnosis and treatment of basal cell and squamous cell carcinomas. Am Fam Physician 2004;70:1481-1488.
  5. Lang PG. Current concepts in the management of patients with melanoma. Am J Clin Dermatol 2002;3:401-426.
  6. Wong CM, Strange RC, Lear JT. Basal cell carcinoma. BMJ 2003;327:794-798.
  7. Sarnaik AA, Weber JS. Recent advances using anti-CTLA-4 for the treatment of melanoma. Cancer J 2009;15(3):169-73.
  8. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with Ipilimumab in patients with metastatic melanoma. N Engl J Med June 5, 2010 (early release e-publication).

Links - Melanoma
Melanoma Patients' Information Page Providing the support and information you need to be a proactive participant in your treatment decisions.

Melanoma Foundation supports medical research for finding effective treatments and eventually a cure for melanoma.

The Melanoma Education Foundation is a grass roots non-profit organization devoted to saving lives from melanoma, a common skin cancer that is often deadly unless detected early before there are any symptoms.

Melanoma Research promotes the exchange of information on all aspects of experimental and clinical research in the field of melanoma.

If you would like to contact us please go to our Contact Page.

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