Kidney Cancer Research Bureau.
Institute of Oncology, Hadassah Medical Moscow.
Am J Clin Oncol. 2021 Apr 1;44(4):137-142. doi: 10.1097/COC.0000000000000797.
Fatigue is one of the most common adverse events of systemic therapy in patients with metastatic renal cell carcinoma (RCC). The aim of multicenter randomized phase 2 study was to determine the efficacy and safety of testosterone in patients with fatigue developed during targeted therapy.
Male patients with metastatic clear-cell RCC, normal prostate-specific antigen level, low testosterone level, and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either testosterone undecanoate (1000 mg) and targeted therapy or targeted therapy alone. The primary endpoint was the mean change of fatigue from baseline to 28 days according to the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary endpoints were safety, Functional Assessment of Cancer Therapy-Kidney Symptom Index 19, testosterone serum concentrations, red blood cell count, and hemoglobin level.
Sixty patients were assigned to receive testosterone and targeted therapy (N=30) or targeted therapy alone (N=30). As of the data cutoff on December 30, 2019, median follow-up was 18.2 months. The study achieved its primary endpoint based on the significant differences at day 28 favoring testosterone over targeted therapy alone regarding the decreased level of fatigue (difference between groups, 22.5 points; 95% confidence interval, 18.4-26.6; P=0.012). Significant changes in scores demonstrating the enhanced quality of life with testosterone compared with targeted therapy were also observed for Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 disease-related symptoms (P=0.01). There were nonsignificant differences in red blood cell count and hemoglobin level between the 2 groups (all P>0.05).
Male patients with metastatic RCC and hypogonadism receiving testosterone had less fatigue and better symptom control during targeted therapy.
疲劳是转移性肾细胞癌（RCC）患者接受全身治疗最常见的不良反应之一。这项多中心随机 2 期研究的目的是确定睾酮治疗接受靶向治疗时出现疲劳的转移性透明细胞 RCC 男性患者的疗效和安全性。
接受一线舒尼替尼或帕唑帕尼治疗的转移性 clear-cell RCC、前列腺特异抗原水平正常、睾酮水平低且无甲状腺功能减退证据的男性患者，出现疲劳后随机（1:1）分配至十一酸睾酮（1000mg）联合靶向治疗组或靶向治疗组。主要终点为根据慢性疾病治疗功能评估-疲劳量表（Functional Assessment of Chronic Illness Therapy-Fatigue scale）自基线至 28 天的疲劳平均变化。次要终点为安全性、癌症治疗功能评估-肾症状指数 19、睾酮血清浓度、红细胞计数和血红蛋白水平。
60 例患者被分配接受十一酸睾酮联合靶向治疗（N=30）或单独靶向治疗（N=30）。截至 2019 年 12 月 30 日数据截止时，中位随访时间为 18.2 个月。研究达到了主要终点，28 天时，与单独靶向治疗相比，睾酮组疲劳水平显著降低（组间差异，22.5 分；95%置信区间，18.4-26.6；P=0.012）。与单独靶向治疗相比，睾酮组在癌症治疗功能评估-肾症状指数 19 疾病相关症状方面也观察到生活质量评分显著改善（P=0.01）。两组的红细胞计数和血红蛋白水平无显著差异（均 P>0.05）。
接受睾酮治疗的转移性 RCC 伴性腺功能减退症的男性患者在接受靶向治疗期间疲劳程度更低，症状控制更好。
