1. Susman, Ed

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WASHINGTON, DC-Men who use sildenafil (Viagra) and other phosphodiesterase 5A inhibitors to counter erectile dysfunction appear to have a possible risk of developing melanoma.

Phosphodiesterase in... - Click to enlarge in new windowPhosphodiesterase inhibitors. Phosphodiesterase inhibitors

In a study that included 525,523 adult men, and after adjusting for age and race, researchers found 36 of 5,307 men who had taken sildenafil were also diagnosed with melanoma-indicating a twofold excess risk of melanoma compared with men not on the phosphodiesterase 5A inhibitors (P<0.001).


Similarly, 30 of 5,933 men who were taking tadalafil (Cialis) also developed melanoma, translating to a 1.6-fold risk of getting the skin cancer (P=0.01), said Peter Boor, MD, who performed the study while a clinical research fellow in dermatology at the Northwestern University, Chicago.


In addition, Boor and his research team also noted eight of 1,117 men who were exposed to vardenafil (Levitra) also developed melanoma, but that relationship fell short of statistical significance (P=0.058).


However, he told Oncology Times the study did not take into consideration other possible confounders. "We are working on a multivariate analysis that would include such things as co-morbidities, sun exposure, and cigarette smoking," he said. He also said his study does not take into account a possible dose response relationship between taking the anti-erectile dysfunction drugs and development of melanoma.


Those missing data points were troubling to Elizabeth Kavaler, MD, a urology specialist at Lenox Hill Hospital, New York City. "There is no detail on how much sildenafil the patients who develop melanoma are taking, and they do not mention concurrent risk factors seen in patients who have erectile dysfunction and who have melanoma," she said.


"Based on the limitations in this paper, I would not counsel patients that Viagra or other phosphodiesterase inhibitors cause an increased risk of melanoma in the men who take it," Kavaler told Oncology Times.


Patients Taking Erectile Dysfunction Drugs

Boor's research team scrutinized the Research on Averse Events And Reports (RADAR) that received funding from the National Institutes of Health and the American Cancer Society and other entities. RADAR includes records of more than 2 million patients. Using hospital codes, the researchers were able to connect the dots between use of the drugs for erectile dysfunction and melanoma. Boor also noted small studies have also suggested a link between the drugs and melanoma.


The phosphodiesterase 5 inhibitors sildenafil, vardenadil, avanafil (Stendra), and tadalafil are all FDA-approved for the treatment of erectile dysfunction and with no caveat regarding melanoma risk in the Full Prescribing Information, Boor said, despite hints at an association in the medical literature.


His search of the database included men who were treated between January 2010 to December 2014, who were exposed to one of the drugs, and who were subsequently documented as diagnosed with melanoma at least 3 months after drug exposure.


"Prospective studies are very important to see whether there is a cause and effect relationship," Boor said in his poster discussion presentation. "Going forward, we really need a prospective study to really tease out this association and establish causality.


"This study underscores how ongoing, proactive, post-marketing pharmacovigilance plays an important role in the detection of adverse outcomes not previously detected as safety signals in already-marketed drugs. Moreover, investigation into causality for any possible relationship between phosphodiesterase 5A inhibition and the development of malignant melanoma is warranted."


He said primary care physicians who are often the prescribers of the drugs should also counsel their patients about skin cancer and melanoma. "I think primary care physicians should always tell their patients to do self-skin examinations," Boor said.


"While not currently recognized as a warning, precaution or possible adverse reaction in the Full Prescribing Information for any one of the drugs, these data indicate a significant association with the development of melanoma in patients taking sildenafil and tadalafil do now warrant exploration to further define this safety signal relative to additional, and even larger, patient populations," he said.


Ed Susman is a contributing writer.