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.

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.