Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex

Abstract

Background: Tuberous sclerosis complex is characterized by the growth of benign tumors in multiple organs, caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. mTOR inhibitors, such as everolimus, are used in patients with tuberous sclerosis complex, mainly to reduce the size of renal angiomyolipomas and subependymal giant cell astrocytomas. There are minimal data available regarding its use during the neonatal period.

Methods: We report clinical and pharmacological data of three neonates treated with the mTOR inhibitor everolimus (two hemodynamically significant cardiac rhabdomyomas and one voluminous subependymal giant cell astrocytoma).

Results: Beneficial clinical responses were observed in all three patients and the medication was generally well-tolerated. Optimal dose was 0.1 mg orally once daily and was confirmed with therapeutic drug monitoring.

Conclusion: Everolimus is a promising pharmacological approach to treat clinically significant inoperable cardiac rhabdomyomas or subependymal giant cell astrocytoma associated with tuberous sclerosis complex during the neonatal period.

Trial registration: ClinicalTrials.gov NCT00789828 NCT01713946.

Keywords: cardiac rhabdomyoma; mTOR inhibitors; subependymal giant cell astrocytoma; tuberous sclerosis complex.