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Efficacy and safety of low-dose everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex

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Abstract

Background

The aim of this study was to evaluate the safety and efficacy of low-dose everolimus treatment in patients with tuberous sclerosis complex (TSC)-associated angiomyolipoma (AML) with renal dysfunction or low body weight.

Methods

We investigated a total of 50 adult patients underwent everolimus treatment for AML associated with TSC. For patients with renal dysfunction (serum creatinine level ≥ 1.5 mg/dl) or low body weight (body weight < 35 kg), 5 mg of everolimus was administered daily (low-dose group). For patients without renal dysfunction or low body weight, 10 mg of everolimus was administered daily (conventional-dose group). The treatment effects and adverse events were compared between the two groups.

Results

There were 20 patients in the low-dose group, and 30 in the conventional-dose group. The average reduction rate of the AML volume in the low-dose group was 52%, whereas it was 60% in the conventional-dose group. No significant differences were found in the average reduction rate between the groups (P = 0.24). The average blood everolimus trough levels were 7.7 ± 3.1 ng/mL in the low-dose group and 12.2 ± 5.7 ng/mL in the conventional-dose group. The level was significantly higher in the conventional-dose group than in the low-dose group (P = 0.004). The incidences of stomatitis and irregular menstruation were significantly lower in the low-dose group than in the conventional-dose group (P = 0.009, P = 0.045, respectively).

Conclusions

The present study demonstrates that low-dose everolimus treatment is safe and effective for TSC-associated AML. This treatment was well tolerated and adverse events were mild in all cases.

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Abbreviations

TSC:

Tuberous sclerosis complex

AML:

Angiomyolipoma

ITSCCC:

International Tuberous Sclerosis Complex Consensus Conference

mTOR:

Mammalian target of rapamycin

TAE:

Transcatheter arterial embolization

ILD:

Interstitial lung disease

eGFR:

Estimated glomerular filtration rate

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Acknowledgements

We thank the patients and their families for participating.

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Authors and Affiliations

  1. Department of Urology, Seirei Yokohama Hospital, Kanagawa, Japan

    Takashi Hatano

  2. Department of Urology, JR Tokyo General Hospital, 2-1-3 Yoyogi Shibuya-ku, Tokyo, 151-8528, Japan

    Takashi Hatano & Katsuhisa Endo

  3. Research Center for Medical Science, Division of Molecular Genetics, The Jikei University School of Medicine, Tokyo, Japan

    Mayumi Tamari

Authors
  1. Takashi Hatano
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  2. Katsuhisa Endo
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  3. Mayumi Tamari
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Contributions

TH participated in the design of the study and drafted the manuscript. KE participated in data acquisition. MT participated in the design of the study and helped to write the paper. All authors read and approved the final manuscript for submission.

Corresponding author

Correspondence to Takashi Hatano.

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The authors of this article declare no conflict of interest.

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Hatano, T., Endo, K. & Tamari, M. Efficacy and safety of low-dose everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex. Int J Clin Oncol 26, 163–168 (2021). https://doi.org/10.1007/s10147-020-01792-w

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  • DOI: https://doi.org/10.1007/s10147-020-01792-w

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