Aminolevulinic Acid Receives FDA Approval to Facilitate Brain Tumor Surgery

On June 6, 2017, the American Food and Drug Administration FDA approved “Aminolevulinic Acid Hydrochloride,” also known as ALA HCI (brand name Gleolan), for patients with grade 3 or 4 gliomas as an optical imaging agent to increase the visibility of cancerous tissue during brain tumor surgery.

Gliomas comprise a heterogeneous group of brain tumors differing in age and sex distribution, growth potential, degree of invasiveness (spread), morphological (structural) features, tendency to progress and response to treatments. The most commonly encountered in adults are high-grade or malignant neoplasms, respectively anaplastic astrocytoma, anaplastic oligodendroglioma and glioblastoma multiforme-GBM. Although treatment options such as radiotherapy and chemotherapy are used for glioma, one of the most important treatments is brain tumor surgery.

You May Be Interested In:

• What are benign and malignant brain tumors? What does brain tumor grade mean? What are the types?

How Does ALA HCI Help Surgeons See Cancerous Areas More Clearly During Brain Tumor Surgery?

ALA HCI is a prodrug (a drug converted by enzymes to its active form after entering the body), absorbed by the body’s cells after oral administration. Enzymes in cells convert it into fluorescent chemicals, particularly protoporphyrin IX (PPIX). Because glioma cells absorb more active substance and convert it to PPIX faster, higher PPIX levels accumulate in cancer cells than in healthy normal tissue. Under blue light of a specific wavelength, healthy normal brain tissue appears blue, while PPIX in the tumor glows an intense red. This enables surgeons to see the tumor more clearly during brain surgery and remove it more accurately while preserving healthy brain tissue.

Studies Leading to Approval

ALA HCI’s efficacy was evaluated in patients aged 18 to 75 with preoperative findings on magnetic resonance imaging (MRI) consistent with World Health Organization Grade 3 or 4 brain tumor glioma diagnosis who underwent surgical resection (tumor removal), across three clinical studies.

Study 1 included 33 patients with newly diagnosed glioma, and Study 2 included 36 patients with recurrent glioma. Study 3 was a randomized multicenter study involving 415 patients diagnosed with high-grade glioma on preoperative MRI.

Across the studies, ALA HCl fluorescence had %78 sensitivity and %68 specificity for correctly identifying tumor boundaries.

ALA HCI’s safety is based on 528 glioma patients in 5 clinical studies. ALA HCI carries risks such as photosensitivity reactions, skin allergies and interpretation errors (false negatives and false positives). Removing more tissue than the tumor actually occupies may increase the short-term risk of serious neurological damage. Side effects occurring in more than % 1 of patients during the week after surgery were fever, low blood pressure (hypotension), nausea and vomiting. During the first 6 postoperative weeks, side effects occurring in fewer than % 1 were chills, photosensitivity reaction, solar dermatitis, hypotension, abnormal liver function tests and diarrhea.

Dosage

The recommended dose of reconstituted ALA HCI solution is administered 3 hours before anesthesia (2-4 hours), at 20 mg/kg. ALA HCI should be used by neurosurgeons who have completed a training program in the use of fluorescence during surgery.

Conclusion

Considering that most brain tumors lack a sharp boundary between tumor and normal tissue, identifying brain tumor margins during surgery can be difficult even for experienced neurosurgeons. ALA HCI aims to help remove as much tumor as possible while preserving healthy brain tissue.