A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic... : Neurosurgery (original) (raw)
RESEARCH—HUMAN—CLINICAL TRIALS
A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent High-Grade Glioma
Cozzens, Jeffrey W. MD; Lokaitis, Barbara C. BA,CCRP; Moore, Brian E. MD; Amin, Devin V. MD,PhD; Espinosa, José A. MD; MacGregor, Margaret MD; Michael, Alex P. MD; Jones, Breck A. MD
*Division of Neurosurgery
‡Center for Clinical Research, Southern Illino-is University School of Medicine, Springf-ield, Illinois
§Department of Pathology, University of Colorado/Anshutz Medical Campus, Aurora, Colorado
Correspondence: Jeffrey W. Cozzens, MD, Division of Neurosurgery, Southern Illinois University School of Medicine, PO Box 19680, Springfield, Illinois 62794-9680. E-mail: [email protected]
Abstract
BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented. This drug has received regulatory approval in Europe but awaits approval in the United States.
OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5-ALA used for enhanced intraoperative visualization of malignant brain tumors, reported from a single medical center in the United States.
METHODS: Prior to craniotomy for resection of a presumed high-grade glioma, individuals were given oral 5-ALA as part of a rapid dose-escalation scheme. At least 3 patients were selected for each dose level from 10 to 50 mg/kg in 10 mg/kg increments. Adverse events, intensity of tumor fluorescence, and results of biopsies in areas of tumor and the tumor bed under white light and deep blue light were recorded.
RESULTS: A total of 19 patients were studied in this phase 1 study. Serious adverse events were unrelated to the ingestion of 5-ALA. At the highest dose level studied (50 mg/kg), 2 out of 6 patients were observed to have transient dermatologic redness and peeling. These were grade 1 adverse events, which were not serious enough to be dose limiting. Patients at higher dose levels (>40 mg/kg) were more likely to have strong tumor fluorescence. There were no instances of false positive fluorescence.
CONCLUSION: The use of 5-ALA for brain tumor fluorescence is safe and effective to a dose of 50 mg/kg. Dose-limiting toxicity was not reached in this study.
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