Low grade gliomas (LGG) are the most common type of pediatric brain tumor (Jones et al., 2017). Depending upon tumor location, many patients undergo surgical resection. If a gross total resection is achieved, patients receive MRI imaging. However, patients who have an incomplete resection or a recurrence receive additional therapy. Young patients with developing brains receive chemotherapy. Older patients may receive radiation. There are multiple agents or combination of agents that are administered in patients with LGG. Standard frontline chemotherapies are either Carboplatin and Vincristine or TPCV (Thioguanine, Lomustine, Procarbazine, and Vincristine). Other traditional single-agent therapies include Temodar, Vinblastine, or Vinorelbine. BRAF/MEK inhibitors (trametinib, dabrafenib, vemurafenib, and selumetinib) are currently being used in clinical trials (Penman, Faulkner, Lowis, & Kurian, 2015).
The MEK inhibitor selumetinib is a single agent oral medication that currently is being trialed within the Pediatric Brain Tumor Consortium (PBTC) for patients with recurrent, relapsed, or progressive LGG. Per Banerjee et al, dose limiting toxicities (DLT) in the phase I trial included grade 3 elevated amylase/lipase, headache, mucositis, and grades 2 to 3 rash at dose levels 1 and 2. Also, dose level 0 (25 mg/m2/dose BID) was more tolerable. The 2-year progression free survival was approximately 69% (Banerjee et al., 2017). In Fangusaro et al, phase II data show a 2-year PFS ranging from 65–96% depending upon patient strata. Common side effects during phase II trials note grade 1-2 CPK elevation, rash, diarrhea, hypoalbuminemia, elevated AST, and rash. Elevated CPK, rash, neutropenia, emesis, and paronychia were rare, but noted grade 3-4 toxicities (Fangusaro et al., 2017). The outcomes to date show promise in patients with low grade gliomas. Currently, randomized trials are being developed to determine if BRAF/MEK inhibitors are more efficacious than standard therapies.
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