New Melanoma Drug: Skin Cancer Treatment Breakthrough?

This week’s issue of the New England Journal of Medicine (NEJM) features an article about an experimental drug for melanoma (called PLX4032).  The lead author of the study is Dr. Keith Flaherty of Massachusetts General Hospital in Boston.

PLX4032—co-developed by Plexxikon and Roche Pharmaceuticals—shows quite promising results against advanced stage melanoma, according to the published results from its Phase I (early phase) clinical drug trial.

According to Daniel DeNoon of WebMD Health News,  “It’s no cure, and it works only for about half of melanoma patients, but a new drug extends progression-free survival in patients dying of advanced melanoma”.

BRAF Gene is the Key

About 50-60% of melanoma sufferers have tumors which can be identified with a specific gene mutation—called the BRAF Gene.

In the PLX4032 study, results showed that an amazing 81% of melanoma patients with the BRAF-gene positively responded to drug treatment. The positive response duration lasted anywhere from 2 to 18 months.  Three of the patients in the study achieved “complete response” status (i.e. no detectable tumor in the body).  (Source: Daniel DeNoon, WebMD Health News, Aug 26, 2010).  However, for melanoma patients who lack the BRAF gene, PLX4032 offers no therapeutic benefit.

PLX4032: Called a Major Breakthrough

According to Dr. Vernon Sondak and Dr. Keiran Smalley (who cowrote an editorial in the NEJM discussing the PLX4032 study):

“These results represent a major breakthrough.  The drug seems to be extremely effective and causes a very high response rate that happens pretty quickly.  It can cause improvement even in people who failed standard treatments. It shows a benefit even in patients with tumors in their livers and other places where traditional treatment bogs down a lot.”

This exciting potential of PLX4032 gives us a chance to highlight some of the key points about malignant melanoma.

Overview of Melanoma

Although there are several types of skin cancer, melanoma is the most lethal type of skin cancer. It is the leading cause of death from skin disease.  In the U.S. this year (2010), it is estimated that there will be 68,000 new cases and 8,700 deaths from melanoma (National Cancer Institute website: What You Need To Know About Melanoma).

It involves cells called melanocytes, which produce a skin pigment called melanin. Melanin is responsible for skin and hair color.

Four Major Types of Melanoma

There are four major types of melanoma: (Source: University of Maryland Medical Center, Dept. of Dermatology)

  • Superficial spreading melanomais the most common type of melanoma. It is usually flat and irregular in shape and color, with different shades of black and brown. It may occur at any age or body site, and is most common in Caucasians.
  • Nodular melanomausually starts as a raised area that is dark blackish-blue or bluish-red. However, some do not have any color.
  • Lentigo maligna melanomausually occurs in the elderly. It is most common in sun-damaged skin on the face, neck, and arms. The abnormal skin areas are usually large, flat, and tan with areas of brown.
  • Acral lentiginous melanomais the least common form of melanoma. It usually occurs on the palms, soles, or under the nails and is more common in African Americans.

Risk Factors for Getting Melanoma

According to mayoclinic.com (Mayo Clinic Staff article), there are 7 major risk factors that would predispose one to develop malignant melanoma:

  • Fair skin.Having less pigment (melanin) in your skin means you have less protection from damaging UV radiation. If you have blond or red hair, light-colored eyes, and you freckle or sunburn easily, you’re more likely to develop melanoma. But melanoma can still develop in people with darker complexions, including Hispanics and blacks.
  • A history of sunburn.One or more severe sunburns as a child or teenager can increase your risk of melanoma as an adult.
  • Excessive ultraviolet (UV) light exposure.Exposure to UV radiation, which comes from the sun and from tanning salons, can increase the risk of skin cancer, including melanoma.
  • Living closer to the equator or at a higher elevation.People living closer to the earth’s equator (such as mid-Africa), where the sun’s rays are more direct, experience higher amounts of UV radiation, as compared with those living in higher latitudes.
  • Having many moles or unusual moles.Having more than 50 ordinary moles on your body indicates an increased risk of melanoma. Also, having an unusual type of mole increases the risk of melanoma. Known medically as dysplastic nevi, these tend to be larger than normal moles and have irregular borders and a mixture of colors.
  • A family history of melanoma.If a close relative, such as a parent, child or sibling, has had melanoma, you have a greater chance of developing it too.
  • Weakened immune system.People with weakened immune systems have an increased risk of skin cancer. This includes people who have HIV/AIDS and those who have undergone organ transplants.

Melanoma Detection: Use Your ABC’s

When it comes to early detection of melanoma, it certainly helps to know your ABC’s, and ‘D’s’:

  • A for Asymmetry
    One half is different than the other half.
  • B for Border Irregularity
    The edges are notched, uneven, or blurred.
  • C for Color
    The color is uneven. Shades of brown, tan,
    and black are present.
  • D for Diameter
    Diameter is greater than 6 millimeters.

If you notice moles or other skin lesions that have the suspicious changes noted above (two or more of the ABCD’s), then it is highly recommended that you see your Family Doctor or Dermatologist to have the lesion evaluated closely.

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