Editorial Comment to Intermittent everolimus administration for renal angiomyolipoma associated with tuberous sclerosis complex.

Abstract

The standard treatment for angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) is changing from invasive surgery to mammalian target of rapamycin inhibitors, including sirolimus and everolimus, in order to preserve patients' renal function.1 Renal complications cause death in 31% of adult patients with TSC.2 TSC is mostly diagnosed during early childhood; however, it is not known whether long-term mammalian target of rapamycin inhibitor use is safe in young patients. Brakemeier et al. published a review of mammalian target of rapamycin inhibitor treatment for TSC patients and emphasized that TSC patients, especially children, have to be closely monitored during the administration of everolimus for the following reasons: (i) most patients with TSC require long-term treatment; (ii) fat-poor renal tumors with a high degree of vascularization, which are difficult to distinguish from renal malignancies, can be presumed to be AML if they show an early response to everolimus treatment; and (iii) the optimal dosage of everolimus for AML in TSC remains unclear.3 The article by Hatano et al. showed for the first time the effectiveness of intermittent everolimus treatment for renal AML associated with TSC.4 After the administration of everolimus, all of the AMLs shrank, and the AMLs in eight out of 26 patients remained smaller after the withdrawal of everolimus. The remaining AML re-grew after the withdrawal of everolimus; however, all of the tumors shrank again after the re-administration of everolimus. Intermittent everolimus treatment might be particularly useful for young patients with AML associated with TSC. Regarding (i), Hatano et al. proposed three advantages of intermittent therapy: (1) it helps to maintain the patient's motivation for treatment by creating a treatment goal; (2) patients are released from adverse events during drug holidays; and (3) unnecessary continuous treatment is avoided, and the economic burden is reduced. Concerning (ii), some studies,5 including the current study, have shown that highly vascularized AML exhibit an early response to everolimus treatment (a 67% tumor reduction in 9 months [median value]), supporting Brakemeier's findings. As for the most important query (iii), intermittent everolimus treatment might be useful for identifying the optimal dose of the drug. Bissler et al. detected an association between the rate of renal tumor shrinkage and trough everolimus levels during continuous everolimus treatment for AML-associated TSC.5 Further study is needed to determine the optimal dose of everolimus, and the optimal duration of the everolimus withdrawal period for AML-associated TSC. None declared.