Study Finds Link Between Melanoma and ED Drugs

Sildenafil

As Sudhir Polisetty explains, new research suggests that sildenafil and other erectile dysfunction medications could increase a man’s risk of melanoma.

Hello, Sudhir Polisetty here with another melanoma blog post. In recent years, troubling findings have been uncovered linking melanoma to erectile dysfunction drugs. PDE5A inhibitors, including sildenafil, Viagra, and other erectile dysfunction drugs could potentially increase the risk of melanoma, but thus far, the study is unable to demonstrate a thorough cause-and-effect relationship.

The study, published in JAMA Internal Medicine, analyzed 25,848 men who enrolled in a Health Professionals’ Follow-up Study. After adjusting for other known risk factors, such as number of moles, natural hair color, family history, and number of sunburns in a lifetime, the study showed that men who had recently used sildenafil were twice as likely to develop melanoma. Those who had used sildenafil in the past, but not recently, showed a slight increased risk. Erectile dysfunction alone, however, didn’t appear to have any significant association to the disease.

The study focused exclusively on the sildenafil contained drug, Viagra, as other erectile dysfunction drugs containing PDE5A inhibitors were unavailable at the start of the study. Investigators assume that tadalafil (Cialis) and vardenafil (Levitra) would produce similar results. In fact, investigators pointed out that because these drugs are longer-acting, the risk for melanoma may even be greater than that from Viagra.

June Robinson, author of an accompanying editorial, believes that a prospective study is necessary before any clinical recommendations are changed. Since the study was retrospective, interpret this information cautiously.

Although melanoma is currently incurable, early detection is key. In 2014 alone, 76,100 cases of melanoma will be diagnosed and 9,710 patients will die from the disease. This being said, in spite of the study’s insufficient findings, a continued investigation should be supported. Physicians may consider performing melanoma screenings before writing prescriptions for erectile dysfunction drugs.

 

You can find more information about the study here: http://www.forbes.com/sites/larryhusten/2014/04/08/study-suggests-link-between-viagra-and-melanoma/

 

Thanks for reading!

Sudhir Polisetty

Learn more about me by viewing my presentations on Slideshare, or read my other dermatology blog posts on WordPress: http://sudhirpolisetty.wordpress.com/blog/

Durable Melanoma Remission Seen With Bristol Immunotherapy Drug

Nivolumab

This diagram shows how Nivolumab works to improve melanoma survival rates.

Welcome back to my melanoma blog. My name is Sudhir Polisetty, and as a General and Surgical Dermatologist I pride myself in keeping up with melanoma breakthroughs. My first blog post focused on Nivolumab, a potential breakthrough melanoma treatment. Recently, I read a follow-up article on this treatment, which has produced lasting remissions in patients with metastatic melanoma.

Typically, melanoma is caused by melanin- forming cells that grow into a malignant tumor. Ultimately, it spreads throughout the body, including the liver, lungs, brain, bones, and lymph nodes.   Bristol-Myers Squibb’s ‘Nivolumab’ works by forcing the body’s own immune system to attack cancer cells.  As part of a greater experiment, Nivolumab and other immunotherapies disable PD-1, which is a protein that stops the immune system from attacking cancer cells. By disabling this protein, also known as the Programmed Death receptor, Nivolumb can continually force the body’s immune system to kill harmful cells.

Dr. F. Stephen Hodi, who heads the study, claims, “the durability of clinical benefit, now with long-term follow-up is fairly remarkable.”  The results of the trial have been published in the Journal of Clinical Oncology, adding that the drug’s effectiveness may be greater in patients whose cases are not so advanced. Bristol Meyers is taking further measures to find a cure by conducting trials using a combination of drugs, as well as testing Nivolumab on other types of cancer such as kidney and lung cancer.

Once diagnosed with melanoma, a patient’s life expectancy plummets to around a year. Thus far, results have shown that 62% of patients were still alive after a year of treatment and 43% after two years of treatment with this drug.  During my residency I witnessed many patients suffering from melanoma, thus my excitement about the potential of Nivolumab. I will be interested to see the data from later-stage trials, as well as if the results can be sustained over a greater length of time.

Learn more in the new report from Reuters: http://www.reuters.com/article/2014/03/03/cancer-melanoma-bristol-idUSL1N0LX1R720140303

 

Thanks for reading,

Sudhir Polisetty

I also write a blog about breakthroughs related to psoriasis. Read my psoriasis blog to learn more, or follow me on Tumblr to find out when I update that blog: sudhirpolisetty.tumblr.com/‎

GSK Reports Results of Late Stage Study

GSK Logo

GlaxoSmithKline recently announced the results of a Phase III study into combining trametinib and dabrafenib. Sudhir Polisetty shares those findings in this blog post.

In my last blog post, I discussed recent studies by GlaxoSmithKline (GSK) into the effectiveness of combining two drugs, Mekinist (trametinib) and Tafinlar (dabrafenib), for treating metastatic or unresectable melanoma. The Food and Drug Administration (FDA) gave accelerated approval for the new drug combination after it showed promise in a Phase I/II study. This approval, however, was dependent on the results of an ongoing late stage (Phase III) trial to assess the drug combination’s clinical benefit in a patient population. Today GSK reported the results of that ongoing study.

GSK announced that its Phase II study, the first of its late stage studies, met its primary endpoint goal of Progression Free Survival. The company added in its release that the observed progression free survival, response rate, and interim overall survival rates were all in line with the values observed in the Phase I/II study that showed so much promise. More specifically, the progression free survival observed among patients using only dabrafenib was greater than the rate seen in previous single agent dabrafenib studies. This led to a more modest difference in the progression free survival between each treatment arm compared to what researchers observed in the Phase I/II study. Among the cohort treated with a combination of trametinib and dabrafenib, the most commonly reported adverse effects were arthralgia (joint pain), pyrexia (fever), chills, diarrhea, fatigue, headache, hypertension, nausea, and vomiting. These are the effects seen in more than 20% of patients in the study.

GSK hopes these initial results, as well as further data to be collected from the study, will increase the body of evidence regarding the efficacy and safety of combining trametinib and dabrafenib for treating melanoma. The combined treatment is approved only for use in the United States in patients with BRAF V600E or K metastatic melanoma.

For more information on this combination of drugs, speak to your dermatologist or read more about GSK’s findings on Reuters: http://uk.reuters.com/article/2014/01/24/us-gsk-cancer-idUKBREA0N0V320140124

Thanks for reading,

Sudhir Polisetty

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GlaxoSmithKline Melanoma Drug Receives Accelerated Approval

GlaxoSmithKline

In this blog post, Sudhir Polisetty shares news about a new melanoma treatment option from GlaxoSmithKline that received accelerated FDA approval.

Welcome back to my melanoma blog, my name is Sudhir Polisetty and I am a dermatologist practicing in New Albany, Indiana. Early this morning, GlaxoSmithKline made headlines with its announcement that a new drug combination for treating melanoma received accelerated approval from United States regulators.

The Food and Drug Administration (FDA) approved two of the company’s drugs, Tafinlar (dabrafenib) and Mekinist (trametinib) to combined use in treating patients with unresectable melanoma or metastatic melanoma with BRAF inhibitors. Unresectable melanoma refers to legions that cannot be surgically removed while metastatic melanoma refers to melanoma that has spread to other parts of the body. BRAF inhibitors, where are mutations of a gene, have proven effective in shrinking melanoma tumors but patients eventually develop resistance to them. While Tafinlar and Mekinist have already been FDA-approved for separate use, GlaxoSmithKline believes melanoma will be held at bay longer by combining the two drugs.

FDA approval came after the drug combination showed promise in a Phase I/II study. Accelerated approval is dependent on the results of the ongoing Phase III trial, which will assess the clinical benefit of this drug combination in a patient population. The randomized Phase I/II open-label study evaluated single-agent dabrafenib (150mg) and the combination of the two drugs as the recommended dose (150/2mg).

Observed overall response rates were 76% for patients treated with the drug combination and just 54% for patients treated with only dabrafenib. The median duration of the response, or how long the results lasted, was 10.5 months for the drug combination and 5.6 months in patients treated with dabrafenib only. These results were supported by analyses conducted by the blinded independent radiologic review committee.

For more on this potential new treatment, take a look at the full press release on Market Watch: http://www.marketwatch.com/story/gsk-gains-accelerated-fda-approval-for-combination-use-of-mekinist-trametinib-and-tafinlar-dabrafenib-2014-01-08?reflink=MW_news_stmp

Thanks for reading,

Sudhir Polisetty

Learn more about me on MD.com, or keep up with other dermatology news by following me on Twitter: https://twitter.com/SudhirPolisetty

Late Stage Melanoma Patients at Risk for Further Melanoma

Melanoma

According to a new study, Stage III & IV melanoma patients could be at greater risk of developing new primary melanomas.

Welcome back to my melanoma news and research blog. My name is Sudhir Polisetty and I am a dermatologist with The Dermatology Center in New Albany. A recent article appearing in the Journal of Clinical Oncology caught my eye. This study, from Lisa Zimmer, MD, of the University Duisburg-Essen’s Department of Dermatology, investigated the incidence of new primary melanomas after diagnosis of Stage III and IV melanoma.

The authors of this study decided to investigate the effects of BRAF inhibitors such as Vemurafenib after clinical trials for such drugs have shown evidence for increased tumor progression and even development of new primary melanomas. Researchers analyzed a total of 7,778 patients diagnosed with Stage III or IV melanoma at Melanoma Institute Australia between 1983 and 2008.

They found that 5% of the 4,215 patients with Stage III Melanoma (295 patients) and 1% of the 3,562 patients with Stage IV Melanoma (43 patients) developed at least one new primary melanoma after the initial diagnosis. Researchers also measured the cumulative incidence rates at six months, one year, and ten years after the initial diagnosis. Incidence rates for Stage III melanoma patients were 1.2%, 1.8%, and 5.9% respectively, while incidence rates for Stage IV melanoma patients were 0.2%, 0.3%, and 0.4%. Male patients and melanoma patients with a history of multiple primaries were especially vulnerable to developing new primary melanomas.

After assessing these results, the researchers concluded that Stage III and IV melanoma patients remain at risk of developing new primary melanomas. Incidence rates were lower than those reported in patients receiving BRAF inhibitors, but since dermatologic assessment is more frequent in BRAF inhibitor trials, we must use caution before comparing these results. Additional studies are needed to get a better idea of the effects of BRAF inhibitors.

You can view the full journal article here: http://jco.ascopubs.org/content/early/2013/12/02/JCO.2013.49.5572.abstract

Thanks for reading,

Sudhir Polisetty

You can learn more about me on my about.me page or learn about other major dermatology news by following me on Tumblr: http://sudhirpolisetty.tumblr.com/

Melanoma of the Oral Cavity

Welcome back to my melanoma blog. Melanoma is primarily known as a type of skin cancer appearing on a patient’s body, which is what most of my posts on this blog have focused on. The New England Journal of Medicine recently detailed the story of a 45-year old Chinese patient who developed a rare type of melanoma in his upper gums.

According to Wei Guo, M.D. and Xin Wang, M.D. of Shanghai and Jiangsu respectively, an otherwise healthy 45-year old man presented with non-painful discoloration of the maxillary gingival. He had no previous history of pigmented skin lesions and said the discoloration had been present for four weeks. Upon further intraoral examination, the lesion was identified as a pigmented macule, 1.5 cm x 4 cm, with asymmetry, multiple colors, and irregular borders. You will hopefully recognize many of these traits from the ABCDE Detection Criteria I introduced in an earlier blog post. Doctors completed a partial removal (maxillectomy) with 2-cm margins but the patient declined radiotherapy and chemotherapy. In a follow-up consultation six months after the partial maxillectomy, doctors reported no signs of tumor recurrence.

In an article appearing on LiveScience.com, Emory University Professor of Pathology Dr. Susan Muller provided additional background on melanoma in the mouth. She completed a study in 2008 investigating the number of melanoma patients treated at Emory University and affiliated hospitals, finding that just eight patients presented with melanoma in the mouth over a 20-year period.

Muller explained that melanoma attacks melanocytes, the cells that produce pigments that influence skin color. She added, “at this point, we don’t know, first, why there are melanocytes in the mouth, and second, what makes those cells go bad and become malignant,” before concluding that patients don’t necessarily have to examine their mouth for possible melanoma, as the risk of oral cancer is much higher. Still, the case serves as a good reminder that melanoma can also occur in the oral cavity.

To view the full article from Live Science, click here: http://www.livescience.com/40304-rare-melanoma-in-gums.html

Thanks for reading,

Sudhir Polisetty

You can learn more about me on my Expertfile profile.

Scientists Identify Melanoma Immunotherapy Targets

"Clinical Cancer Research"

A new study on potential immunotherapy targets for melanoma appeared in the American Association of Cancer Research’s medical journal, Clinical Cancer Research.

Welcome back to my melanoma blog. Today I want to focus on immunotherapy, which is defined as the treatment of disease by suppressing, enhancing, or inducing a response from the body’s immune system. In order to use this method for treating melanoma, physicians must be able to identify appropriate target antigens. According to a new study appearing in the American Association of Cancer Research’s Clinical Cancer Research, researchers might have identified seven potential candidate genes.

Researchers used a highly sensitive technology called NanoString to simultaneously measure multiple genes seen in higher quantities in tumor cells than normal cells. The NanoString works by isolating genetic material called RNA from tumor samples, allowing researchers to compare RNA levels in tumor samples with RNA levels in normal tissue samples. The researchers designed a NanoString probeset that contained 97 genes, including 72 considered possible candidate genes for immunotherapy. This technology profiled and analyzed five established melanoma cell lines, 59 resected metastatic melanoma tumors, and 31 normal tissue samples.

Of the 72 potential melanoma immunotherapy target genes, 33 were overexpressed in more than 20% of the melanoma tumor samples studied while ANOVA analysis found 20 genes differentially expressed between normal tissues and tumor samples. Finally, researchers analyzed normal tissue gene expression and identified seven genes with limited normal tissue expression that it recommends for further consideration as possible immunotherapy target antigens. These seven genes are CSAG2, MAGEA3, MAGEC2, IL13RA2, RAME, CSPG4, and SOX10. The first five genes mentioned belong to the cancer-testis gene family while the remaining two are melanoma-related genes.

According to Richard Morgan, PhD, who served as one of the study’s authors, further investigation is needed before immune cells engineered to target these markers can be used in patients.  Hopefully in time these immunotherapy agents can increase the number of patients eligible for adoptive immunotherapy.

Learn more about this study by viewing the research team’s press release: http://medicalxpress.com/news/2013-09-scientists-melanoma-immunotherapy.html

Thanks for reading,

Sudhir Polisetty

To read articles specifically about melanoma, visit my WordPress blog.

Preventing Melanoma

Melanoma prevention tips

By following recommended prevention tips, you can decrease your chances of developing melanoma.

Welcome back to my melanoma blog. The New York Daily News recently wrote an article about melanoma, shedding light on some facts about the disease as well as how to prevent, detect, and treat it. I have already discussed how to use the ABCDE Detection system to determine when to consult a dermatologist about your mole but I have not addressed prevention tips.

As the New York Daily News article notes, the exact cause of melanoma is unclear but we do know many contributing factors. Family history and excessive exposure to UV rays (via natural sunlight, tanning beds, or lamps) can both increase an individual’s risk of developing melanoma. Other risk factors are:

  • Living in high altitude areas or locations close to the equator
  • Long-term UV ray exposure
  • One or more instances of blistering sunburn during childhood
  • Owning freckled or fair skin
  • Spending lots of time outside but not using sun protection
  • Exposure to carcinogens such as arsenic, creosote, and coal tar
  • Possessing multiple moles, specific types of moles, or many birthmarks
  • Having a weakened immune system due to other medical conditions or medications used to treat those conditions

Melanoma should ideally be identified early, so it is important to perform routine self-examination of your skin and moles. The American Cancer Society recommends professional skin examinations every three years for individuals aged 20-40 and annual examinations for anyone over 40. The article also suggests the following melanoma prevention tips:

  • Steer clear of tanning beds or lamps
  • Avoid excessive sun exposure, especially between 10 AM and 4 PM
  • Wear sunglasses to protect your eyes (as melanoma can occur in the pigmented area of the eyes)
  • Apply sunscreen 15-30 minutes before going outdoors and reapply every 2 hours, especially if sweating
  • Protect against UV rays by wearing hats and protective clothing
  • Consult a dermatologist if you notice any changes in your skin or a mole

Thanks for reading,

Sudhir Polisetty

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Can Tattoos Hide Moles and Melanoma?

Melanoma within tattoo

In this image, from eScholarship.org, a malignant tumor is obscured by a cosmetic tattoo.

Welcome back to my melanoma blog. I created this blog to showcase interesting research and trends related to dermatology. While many of my posts thus far have focused on medical research, I will switch gears this week to address a growing trend: the discovery of melanoma within tattoos.

A recent article appearing in JAMA Dermatology investigated pitfalls and recommendations in cases of laser removal of decorative tattoos with pigmented lesions. Researchers described 16 cases of malignant melanoma developing in tattoos, including one where a man who wanted to remove large, multi-colored tattoos located on his chest and arms attempted laser removal therapy. The man’s physician noticed a suspicious mole inside the right arm tattoo and recommended removal. The patient refused to have the mole removed and began laser treatments. Doctors told the man seven years later that he could not continue treatments until he had the mole removed; the mole turned out to be Stage II Melanoma.

Roughly 1 in 4 Americans ages 18-50 currently has at least one tattoo and 75,000 Americans are diagnosed with melanoma each year. It is possible that many Americans with melanoma do not know that they have it because it is hidden by a tattoo. This is especially problematic as the longer melanoma goes undetected; the more difficult it becomes to treat. Individuals with existing moles should look out for the ABCDE features that I detailed in my last blog post and check them frequently, as a large and colorful tattoo could obscure Color variations or make it harder to notice mole Evolution.

If you are thinking about getting a tattoo, make sure it is applied to a section of the skin free of moles or birthmarks. You can even have a dermatologist check the planned tattoo area beforehand. Alternatively, when removing tattoos through laser therapy, have a dermatologist evaluate the tattoo area before beginning removal procedures.

 

For more information on this study, view Harvard Medical School’s summary of the researchers’ findings: http://www.health.harvard.edu/blog/tattoos-moles-and-melanoma-201308056578

 

Thanks for reading,

Sudhir Polisetty

 

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Children with Melanoma did not Meet ABCDE Detection Criteria

Welcome back to my melanoma blog. Melanoma, defined as a malignant tumor made up of melanocytes, is the most dangerous type of skin cancer. Patients and dermatologists detect melanoma using the ABCDE detection criteria, which is a mnemonic device signifying:

  • Asymmetrical shape: melanoma lesions are irregularly shaped while benign moles are symmetrical.

  • Border: non-cancerous moles have even borders while melanoma lesions have irregular borders.

  • Color: the presence of more than one color or uneven distribution of color serves as a warning sign as benign moles are generally a single shade of brown.

  • Diameter: melanoma lesions are typically more than 6 mm in diameter.

  • Evolution/Enlarging: individuals should consult with a doctor if moles have recently grown larger or changed color.

recent study by researchers at the University of California, San Francisco sought to determine whether these criteria are able to effectively recognize melanoma in children. Researchers studied children diagnosed with melanoma before the age of 20 between 1984 and 2009 at the University of California, San Francisco. These patients were then divided into two age groups: 1-10 years (Group A) and 11-19 years old (Group B).

The research group found that 60% of the patients in Group A and 40% of the patients in Group B did not meet conventional ABCDE criteria. In all, 44% of those studied were histopathologically unclassifiable using existing melanoma subtypes. More common melanoma indicators included amelanosis (lack of pigments), bleeding, bumps, uniform color, variable diameter, or de novo development (arising without a precursor lesion).

Researchers concluded that the current method for detecting melanoma (the ABCDE criteria) is inadequate for children. They recommend using conventional ABCDE criteria in conjunction with the following new ABCD detection criteria: Amelanotic, Bleeding, Bump, Color uniformity, De novo, and any Diameter.

Find out more about the study in the Journal of the American Academy of Dermatology: http://www.sciencedirect.com/science/article/pii/S0190962212023328

Thanks for reading,

Sudhir Polisetty

ABCDE criteria

The ABCDE Criteria help individuals and their doctors improve early detection of melanoma.

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