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The FDA ( Food and Drug Administration ) has granted accelerated approval to Everolimus ( Afinitor ), an mTOR inhibitor, for patients with subependymal giant cell astrocytoma ( SEGA ) associated with tuberous sclerosis ( TS ) who require therapy but are not candidates for surgical resection. Afinitor was originally approved in March 2009 for the treatment of adult patients with advanced renal cell carcinoma ( RCC ) whose disease was resistant to Sunitinib or Sorafenib.

The efficacy and safety of Everolimus in patients with SEGA was demonstrated in a single-arm open-label clinical trial. Twenty-eight patients whose SEGA lesions had demonstrated evidence of growth on serial imaging received Everolimus orally once daily at a starting dose of 3 mg/m2/day with subsequent titration to a whole blood concentration of 5-15 ng/mL. The median age was 11 years ( range 3-34 ), 61% were male, and 86% were Caucasian. The primary efficacy endpoint was reduction in the volume of the primary SEGA lesion at 6 months. The median duration of treatment on this trial was 24.4 months ( range 4.7-37.3 months ).

Nine of 28 patients ( 32% ) had a 50% reduction or greater in the volume of their largest SEGA lesion at 6 months. Three of the four patients with a history of prior surgery had more than a 50% reduction in tumor volume. Median response duration for the nine patients who responded was 266 days ( range 97 to 946 days ). No complete responses were observed.

All patients experienced at least one adverse event. The most common adverse events ( incidence of at least 30% ) included stomatitis, upper respiratory tract infections, sinusitis, otitis media, and pyrexia. Grade 3 adverse reactions were reported in 36% of patients and included convulsion, infections ( sinusitis, pneumonia, tooth infection, and viral bronchitis ), stomatitis, aspiration, cyclic neutropenia, sleep apnea syndrome, vomiting, dizziness, white blood cell count decreased, and neutrophil count decreased. Convulsions ( grade 4 ) were noted in a single patient. No deaths were observed during the study.

Laboratory abnormalities ( seen in than 30% of patients ) included transaminase elevations, hypercholesterolemia and hypertriglyceridemia, leukopenia, anemia, and hyperglycemia.

Live vaccines and close contact with those who have received live vaccines should be avoided.

The recommended starting dose of Everolimus for this indication is based on body surface area as shown in the following table with subsequent titration to attain a blood trough concentration of 5-10 ng/mL.
Recommended starting dose of Everolimus for treatment of patients with SEGA is the following: body surface area ( BSA ) 0.5 m2-to-1.2 m2, starting dose: 2.5 mg once daily; BSA: 1.3 m2-to-2.1 m2, starting dose: 5 mg once daily; BSA greater than or equal to 2.2 m2, starting dose: 7.5 mg once daily.

Source: National Cancer Institute, 2010


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