Efficacy and safety of postoperative adjuvant mitotane therapy in adrenocortical carcinoma at high risk of recurrence
10.3760/cma.j.cn112330-20241112-00501
- VernacularTitle:高复发风险肾上腺皮质癌术后米托坦辅助治疗的疗效及安全性
- Author:
Yi LIU
1
;
Zhan WANG
1
;
Jiayang CHEN
1
;
Jianhua DENG
1
;
Weifeng XU
1
;
Songchen HAN
1
;
Yanan LI
1
;
Xu WANG
1
;
Yang ZHAO
1
;
Yushi ZHANG
1
Author Information
1. 中国医学科学院北京协和医学院北京协和医院泌尿外科，北京 100730
- Publication Type:Journal Article
- Keywords:
Adrenal cortex neoplasms;
Carcinoma;
Mitotane;
Efficacy;
Safety;
Prognosis
- From:
Chinese Journal of Urology
2025;46(1):5-9
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.
