SAN FRANCISCO – Voriconazole increased the risk of squamous cell carcinoma by 73% in a review of 455 lung transplant patients at the University of California, San Francisco.
The increase was for any exposure to the drug after transplant (adjusted hazard ratio, 1.73; P = .03). The investigators also found that each additional 30-day exposure at 200 mg of voriconazole twice daily increased the risk of squamous cell carcinoma (SCC) by 3.0% (HR, 1.03; P < .001). The results were adjusted for age at transplant, sex, and race. Overall, SCC risk was highest among white men aged 50 years or older at the time of transplant.
Although voriconazole did protect against posttransplant Aspergillus colonization (aHR, 0.50; P < .001), it did not reduce the risk of invasive aspergillosis. The drug reduced all-cause mortality only among colonized subjects (aHR, 0.34; P = .03), and offered no mortality benefit among those who were not colonized.
There was no difference in all-cause mortality between patients who had any exposure to voriconazole and those who did not, “but we actually found a 2% increased risk of death for each 1 month on the medication. Patients who weren’t colonized were the ones contributing to this increased risk of death,” said lead investigator Matthew Mansh, now a medical student at Stanford (Calif.) University.
There was no increased risk of SCC with alternative antifungals, including inhaled amphotericin and posaconazole. These alternatives should be considered instead of voriconazole in people at higher risk for skin cancer after lung transplants, according to the study, Mr. Mansh noted.
Voriconazole, which is widely used for antifungal prophylaxis after solid organ transplants, has been linked to skin cancer. The reason for the carcinogenic effect is not known; researchers are working to unravel the molecular mechanisms.
“Physicians should be cautious when using voriconazole in the care of transplant recipients. If you see a patient who is developing phototoxicity” with voriconazole, “and if they don’t have evidence of Aspergillus colonization, you may want to limit exposure to high doses of this drug or suggest an alternative,” Mr. Mansh said.
“We have now demonstrated that the alternatives “don’t carry this increased risk of cutaneous SCC,” Mr. Mansh said at the American Academy of Dermatology annual meeting.
The mean age of the study patients at transplant was 52 years, and the majority of patients were white; slightly more than half were men. Most had bilateral lung transplants, with pulmonary fibrosis at the leading indication.
Voriconazole was used in 85% of the patients for an average of 10 months. A quarter of voriconazole patients developed SCC within 5 years of transplant, and 43% within 10 years. Among patients who did not receive the drug, 15% developed SCC within 5 years of transplant, and 28% developed SCC within 10 years of transplant.
“The benefit of voriconazole in terms of death was limited to patients with evidence of Aspergillus colonization, and it wasn’t dose dependent. Patients who had a higher cumulative exposure did not get more benefit,” Mr. Mansh said.
Mr. Mansh had no relevant disclosures.