Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation.
Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post-transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time-dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.
Department of Medicine, University of California, San Francisco, CA, USA.
Nicholas A
http://orcid.org/0000-0002-4586-959X
NA
Kolaitis
Department of Medicine, University of California, Los Angeles, CA, USA.
Erin
E
Duffy
David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Alice
A
Zhang
David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Michelle
M
Lo
David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
David T
DT
Barba
Department of Medicine, University of California, Los Angeles, CA, USA.
Meng
M
Chen
Division of Dermatology, University of California, Los Angeles, CA, USA.
Teresa
T
Soriano
Division of Dermatology, University of California, Los Angeles, CA, USA.
Jenny
J
Hu
Department of Surgery, University of California, Los Angeles, CA, USA.
Vishad
V
Nabili
Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA.
Rajeev
R
Saggar
Department of Medicine, University of California, Los Angeles, CA, USA.
David M
DM
Sayah
Department of Medicine, University of California, Los Angeles, CA, USA.
Ariss
A
DerHovanessian
Department of Medicine, University of California, Los Angeles, CA, USA.
Michael Y
MY
Shino
Department of Medicine, University of California, Los Angeles, CA, USA.
Joseph P
JP
Lynch
Department of Medicine, University of California, Los Angeles, CA, USA.
Bernie M
BM
Kubak
Department of Surgery, University of California, Los Angeles, CA, USA.
Abbas
A
Ardehali
Department of Medicine, University of California, Los Angeles, CA, USA.
David J
DJ
Ross
Department of Medicine, University of California, Los Angeles, CA, USA.
John A
JA
Belperio
Department of Medicine, University of California, Los Angeles, CA, USA.
David
D
Elashoff
Department of Medicine, University of California, Los Angeles, CA, USA.
Rajan
R
Saggar
Department of Medicine, University of California, Los Angeles, CA, USA.
S Samuel
SS
Weigt
D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced*; D005260:Female; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced*; D013997:Time Factors; D065819:Voriconazole / Q000009:adverse effects*
D000935:Antifungal Agents; D065819:Voriconazole
complications (lung clinical); fungal (infection); quality of life (quality of life, ethics, economics); solid tumor (malignancy and long-term complications)