Effects of everolimus on tuberous sclerosis complex‐associated renal angiomyolipoma: A preliminary report

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Tuberous sclerosis complex (TSC) presents with multisystem benign neoplasm induced by dysregulation of the mammalian target of rapamycin (mTOR) pathway.1 The common phenotype is seizures in childhood and the characteristic feature of intracranial lesions prompts the clinicians to make a diagnosis.2 However, some may be asymptomatic in childhood until renal angiomyolipoma (AML) and chest lymphangioleiomyomatosis associated symptoms occur.5 With the development of diagnostic tools, the 2012 International TSC consensus conference recommended patients undergo regular surveillance regardless of age and lesion size, to minimize potentially comorbidities.6
Renal AML in TSC is usually asymptomatic but may progress during adulthood. In a previous study assessing mortality associated with TSC, renal problems (renal failure or tumoural complications, retroperitoneal haemorrhage, and metastases of renal cell carcinoma) in TSC were the second leading cause of premature death after severe intellectual disability.7 Disease mortality is associated with aneurysms and haemorrhage‐prone renal AML and worsening outcomes are associated with progressive increases in size.8 Thus, current guidelines recommend magnetic resonance imaging (MRI) of the abdomen to assess the progression of renal AML and renal cystic disease every 1‐3 years throughout the patient's lifetime.6
For patients with renal AML presenting with acute haemorrhage, embolization followed by corticosteroids is the first‐line therapy and nephrectomy is avoided as far as possible. Moreover, selective embolization or kidney‐sparing resection is acceptable as a second‐line therapy for asymptomatic renal AML. Recently, for asymptomatic renal AML measuring larger than 3 cm in diameter, treatment with mTOR inhibitors is the recommended first‐line therapy.6
Recently, studies demonstrate that mTOR inhibitors such as sirolimus are effective in reducing renal AML mass volume in patients with TSC and have an acceptable and tolerable safety profile.10 Everolimus has been approved for the treatment of patients with TSC‐associated AML who did not require immediate surgery. The improved pharmacokinetic profile of everolimus over sirolimus makes it an attractive, non‐invasive option for patients. The Everolimus for Angiomyolipoma Associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis (EXIST‐2) trial has confirmed the effectiveness of everolimus in reducing TSC‐associated AML volume.11 An oral everolimus 10 mg daily resulted in a significant reduction in the sum of all target renal AML volumes ≥50% relative to baseline, and most adverse events reported were mild to moderate in severity.11 This study aimed to examine the effectiveness and its contingent effects of low cost and less adverse events of low dose of everolimus in comparison to high dose used in EXIST‐2 trial in reducing TSC‐associated renal AML mass volume.

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