Safety of hexaminolevulinate for blue light cystoscopy in bladder cancer. A combined analysis of the trials used for registration and postmarketing data.
OBJECTIVE
To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience.


METHODS
Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed.


RESULTS
In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% and 58% of the patients had at least 1 adverse event (AE), although predominantly mild to moderate. The majority was considered as not related to HAL-BLC and reported in the urinary tract. No serious adverse events (SAEs) were considered definitely related to HAL-BLC, but in 6 patients serious AEs were of an uncertain relationship. Four possibly related hypersensitivity reactions have been reported. Repeated use did not reveal additional toxicity, also supported by data from 3 European centers.


CONCLUSIONS
This combined and detailed analysis of patients from 6 HAL-BLC studies with very comparable criteria shows that HAL-BLC is safe and poses very little additional risks other than expected for WL cystoscopy for bladder tumor resection in this specific patient population. This is supported by 9 years of postmarketing experience. Repeated use also seems safe.
Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address: f.witjes@uro.umcn.nl.
J Alfred
JA
Witjes
Department of Urology, Thomas Jefferson University, Philadelphia, PA.
Leonard G
LG
Gomella
Department of Urology, Eberhard-Karls University, Tübingen, Germany.
Arnulf
A
Stenzl
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN.
Sam S
SS
Chang
Department of Urology, Clinic Traunstein, Traunstein, Germany.
Dirk
D
Zaak
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX.
H Barton
HB
Grossman
D000368:Aged; D000622:Aminolevulinic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D018849:Controlled Clinical Trials as Topic; D003558:Cystoscopy / Q000379:methods*; D017277:Drug Approval; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D011358:Product Surveillance, Postmarketing; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*
D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester