scholarly journals Mutational analysis of renal angiomyolipoma associated with tuberous sclerosis complex and the outcome of short-term everolimus therapy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jianxin Ni ◽  
Fengqi Yan ◽  
Weijun Qin ◽  
Lei Yu ◽  
Geng Zhang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Term Therapy ◽  
Renal Angiomyolipoma ◽  
Efficacy And Safety ◽  
Short Term

Abstract To identify clinical characteristics and mutation spectra in Chinese patients with renal angiomyolipoma (AML) associated with the tuberous sclerosis complex (TSC, TSC-AML), examined the efficacy and safety of short-term everolimus therapy (12 weeks). We analyzed the frequency distribution of each TSC-related clinical feature and investigated gene mutations by genetic testing. Some subjects received everolimus for 12 weeks at a dose of 10 mg/day, and the efficacy and safety of short-term everolimus therapy were examined. Finally, 82 TSC-AML patients were enrolled for analysis in this study. Of the 47 patients who underwent genetic testing, 22 patients (46.81%) had at least one detectable mutation in the TSC1 or TSC2 gene: 7 were TSC1 gene mutations, 13 were TSC2 gene mutations, and 2 were found in both TSC1 and TSC2. Everolimus treatment had a statistically significant effect on the renal AML volume reduction during follow-up (P < 0.05), and the mean reduction rate of volume for all cases was 56.47 ± 23.32% over 12 weeks. However, 7 patients (7/25; 28.00%) experienced an increase in renal AML tumor volume within 12 weeks after discontinuation of the everolimus treatment. Although most patients (27/30, 90.00%) experienced some adverse events during the treatment period, all such events were mild, and no patients discontinued or needed dose reduction because of adverse events. Overall, in this study, the mutation rate of TSC-AML patients is much lower than other reports. Short-term everolimus treatment for TSC-AML is effective and safe, but the stability is much lower than long-term therapy.

scholarly journals Low-Dose Everolimus Maintenance Therapy for Renal Angiomyolipoma Associated With Tuberous Sclerosis Complex

2021 ◽  
Vol 8 ◽  
Author(s):  
Cong Luo ◽  
Wen-Rui Ye ◽  
Xiong-Bin Zu ◽  
Min-Feng Chen ◽  
Lin Qi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Tuberous Sclerosis ◽  
Induction Therapy ◽  
Tuberous Sclerosis Complex ◽  
Low Dose ◽  
Standard Dose ◽  
Gene Mutations ◽  
Renal Angiomyolipoma ◽  
Significance Level

Objective: To assess the safety and efficacy of low-dose everolimus maintenance therapy for tuberous sclerosis complex-related renal angiomyolipoma (TSC-RAML) patients that had previously undergone standard-dose treatment for a minimum of 6 months.Materials and Methods: In total, 24 patients with a definitive TSC diagnosis were enrolled from April 2018 – April 2019 at Xiangya Hospital, Central South University. All patients underwent low-dose everolimus maintenance therapy following standard-dose everolimus induction therapy for a minimum of 6 months. Patients additionally underwent TSC1/TSC2 genetic testing, And they were followed-up at 3, 6, 12, 18, and 24 months. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were used to monitor patient RAML responses, while adverse events (AEs) were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). P &lt; 0.05 was the significance level for all analyses, which were performed using SPSS 19.0.Results: TSC1/TSC2 gene mutations were present in all 24 patients, all of whom achieved a significant reduction in TSC-RAML volume within the initial 6-month induction therapy period, and exhibited volume stabilization during the low-dose maintenance therapy treatment period without any instances of TSC-RAML regrowth. Adverse events (AEs) were significantly less severe and less frequent over the course of maintenance therapy relative to standard therapy.Conclusions: Low-dose everolimus maintenance therapy represents an effective approach to achieving TSC-RAML control following a minimum of 6 months of full-dose induction therapy, and may be associated with decreases in everolimus-related AE frequency and severity.

PD17-01 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EXIST-2 LONG-TERM EFFICACY AND SAFETY

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
John Bissler ◽  
J. Christopher Kingswood ◽  
Elzbieta Radzikowska ◽  
Bernard A. Zonnenberg ◽  
Michael Frost ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Renal Angiomyolipoma ◽  
Efficacy And Safety ◽  
Term Efficacy

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

2020 ◽  
Author(s):  
Takashi Hatano ◽  
Katsuhisa Endo ◽  
Mayumi Tamari
Keyword(s):  
Body Weight ◽  
Adverse Events ◽  
Renal Dysfunction ◽  
Tuberous Sclerosis Complex ◽  
Dose Group ◽  
Low Dose ◽  
Reduction Rate ◽  
Renal Angiomyolipoma ◽  
Efficacy And Safety ◽  
Conventional Dose

Abstract Background: Tuberous sclerosis complex (TSC) is a rare disease, with an autosomal dominant mode of inheritance, that results in systemic hamartoma. Renal angiomyolipoma (AML) is observed in 50-80% of TSC patients. Everolimus is recommended as an initial treatment for TSC-associated AML; however, few studies have investigated the efficacy and safety of low-dose everolimus therapy. In the present study, we evaluated the safety and efficacy of low-dose everolimus treatment in patients with TSC-associated AML with renal dysfunction or low body weight.Methods: From January 2014 through December 2018, 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 (graded according to the Common Terminology Criteria for Adverse Events v5.0–JCOG) 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. Based on our results, low-dose everolimus can be considered a treatment option for patients with TSC-associated AML, especially for those who have renal dysfunction or low body weight.

scholarly journals Everolimus Versus Sirolimus for Angiomyolipoma Associated with Tuberous Sclerosis Complex: A Multi-Institutional Retrospective Study in China

2021 ◽  
Author(s):  
luo cong ◽  
Yu-shi Zhang ◽  
Ming-Xin Zhang ◽  
Min-Feng Chen ◽  
Yuan Li ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Adverse Events ◽  
Tuberous Sclerosis ◽  
Oral Mucositis ◽  
Tuberous Sclerosis Complex ◽  
National Cancer Institute ◽  
Therapeutic Efficacy ◽  
Efficacy And Safety ◽  
First Choice ◽  
Significant Difference

Abstract Purpose To evaluate the efficacy and safety of everolimus and sirolimus in patients with tuberous sclerosis complex-associated angiomyolipomas (TSC-AML). Materials and Methods We performed a multi-institutional retrospective study of TSC-AML patients treated with oral everolimus or sirolimus. Angiomyolipoma volume was estimated using orthogonal measurements by MRI or CT. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events. All analyses were performed using SPSS 19.0 software. Results There were high response rates in both two groups. With the prolonged medication time, the therapeutic efficacy of two agents became more significant. Everolimus had a more significant TSC-AML volume reduction after 6 and 12 months than sirolimus. More than 1/2 of everolimus patients had ≥ 50% reduction and approximately 80% of them had ≥ 30% reduction, higher than that of the sirolimus patients. Regarding safety, there was no significant difference in the incidence of AEs between the two groups. And the most common AE was oral mucositis. Conclusions Both everolimus and sirolimus are excellent therapeutic choices for TSC-AML. However, everolimus had a better therapeutic efficacy than sirolimus, especially in reducing TSC-AML volume. Therefore, everolimus is recommended as the first choice.

Novel TSC1 and TSC2 gene mutations in Chinese patients with tuberous sclerosis complex

2017 ◽  
Vol 154 ◽  
pp. 104-108 ◽  
Author(s):  
Tingting Yu ◽  
Yingzhong He ◽  
Niu Li ◽  
Yunqing Zhou ◽  
Zhiping Wang ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Mutations ◽  
Chinese Patients ◽  
Tsc2 Gene
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