Comprehensive Cancer Center.
Departments of Internal Medicine.
Am J Clin Oncol. 2021 Jun 1;44(6):239-246. doi: 10.1097/COC.0000000000000814.
Preclinical studies with muscadine grape extract (MGE) show antitumor activity and decreased systemic inflammation. This phase I study (NCT02583269) assessed safety and tolerability of a proprietary MGE preparation in patients with advanced solid tumors.
Patients with metastatic or unresectable cancers who were progressing on standard therapies were assigned to MGE in a standard 3+3 design. Five dose levels were tested (320 to 1600 mg total phenolics/d). Safety and maximum-tolerated dose were assessed after 4 weeks. Patients were evaluated for response at 8 weeks and continued on MGE if clinically stable. Secondary outcomes were response, survival, adherence, fatigue, and quality of life (QOL).
In total, 23 patients (lung, n=7; gastrointestinal, n=7; genitourinary, n=6; other, n=3) received MGE capsules by mouth twice daily. The cohort [median age 72 years, 48% Eastern Cooperative Oncology Group (ECOG) 2] was heavily pretreated. After 4 weeks on MGE, possibly attributable adverse events grade 2 or higher were fatigue (n=1), decreased lymphocyte count (n=1), and constipation (n=2), including 1 dose-limiting toxicity for grade 3 constipation. Maximum-tolerated dose was not reached. No partial responses were observed. Median time on therapy was 8 weeks, with 29% of patients treated beyond 16 weeks and a median overall survival of 7.2 months. QOL and fatigue levels were stable from baseline to 8 weeks. Higher MGE dose was correlated with improvement in self-reported physical well-being QOL at 8 weeks (r=0.6; P=0.04).
MGE is safe and well-tolerated in heavily pretreated and older cancer patients. The potential anticancer properties and the effects of MGE on physical well-being and QOL metrics will be evaluated in future studies.
从临床前研究来看，麝香葡萄提取物（MGE）具有抗肿瘤活性和降低全身炎症的作用。这项 I 期研究（NCT02583269）评估了一种专利 MGE 制剂在晚期实体瘤患者中的安全性和耐受性。
正在接受标准治疗且疾病进展的转移性或不可切除癌症患者，按标准 3+3 设计方案入组 MGE。共测试了 5 个剂量水平（总酚类 320 至 1600mg/d）。4 周后评估安全性和最大耐受剂量。8 周时评估患者的反应，如果临床稳定，则继续使用 MGE。次要结局包括反应、生存、依从性、疲劳和生活质量（QOL）。
共有 23 名患者（肺癌 7 例，胃肠道癌 7 例，泌尿生殖系统癌 6 例，其他癌 3 例）每天口服 MGE 胶囊两次。该队列[中位年龄 72 岁，48%东部肿瘤协作组（ECOG）2 级]患者接受了大量的预处理。MGE 治疗 4 周后，可能与药物相关的不良事件为 2 级或更高级别的疲劳（n=1）、淋巴细胞计数减少（n=1）和便秘（n=2），包括 1 例剂量限制性毒性为 3 级便秘。未达到最大耐受剂量。未观察到部分缓解。中位治疗时间为 8 周，29%的患者治疗时间超过 16 周，中位总生存期为 7.2 个月。从基线到 8 周，QOL 和疲劳水平保持稳定。更高的 MGE 剂量与 8 周时自我报告的身体整体健康状况 QOL 改善相关（r=0.6；P=0.04）。
MGE 在接受大量预处理和老年癌症患者中是安全且耐受良好的。未来的研究将评估 MGE 的潜在抗癌特性以及对身体整体健康状况和 QOL 指标的影响。
