Zhang Qi, Deng Ting, Yang Fen, Guo Weijian, Liu Dan, Yuan Jiajia, Qi Changsong, Cao Yanshuo, Yu Qiuqiong, Cai Huiming, Peng Zhi, Wang Xicheng, Zhou Jun, Lu Ming, Gong Jifang, Li Jian, Ba Yi, Shen Lin
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Front Pharmacol. 2022 Jul 22;13:833583. doi: 10.3389/fphar.2022.833583. eCollection 2022.
Simmitecan is a potent inhibitor of topoisomerase I with anti-tumor activity. This phase Ib trial was conducted to investigate the safety and anti-tumor effect of simmitecan alone or in combination with other drugs. Eligible patients with advanced solid tumor had no further standard treatment options. Patients were allocated to receive simmitecan alone, simmitecan in combination with 5-fluorouracil (5-FU)/leucovorin (LV), or simmitecan in combination with thalidomide, 14 days a cycle, until disease progression or unacceptable toxicity occurred. A total of 41 patients were enrolled, with a median age of 55 (range 29-69) years. Among them, 13 patients received simmitecan monotherapy, 10 received simmitecan + 5-FU/LV, and 18 received simmitecan + thalidomide. No dose-limiting toxicity occurred. Overall, the most common grade 3/4 adverse event (AE) was neutropenia (46.2, 70.0, and 88.9%, respectively, in simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts), and treatment-related severe AEs included anemia and febrile neutropenia (7.7% each in simmitecan cohort), diarrhea (10% in simmitecan +5-FU/LV cohort), and febrile neutropenia (5.6% in simmitecan + thalidomide cohort). The majority of patients (24/41, 58.3%) had progressed on prior irinotecan; nevertheless, partial response was achieved in one colorectal cancer patients treated with simmitecan + thalidomide. The disease control rates of simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts were 46.2, 80.0, and 61.1%, respectively. This study demonstrated a manageable safety profile of simmitecan as a single agent or as part of a combination therapy. There have not been any safety concerns with simmitecan in combination when compared to simmitecan alone. Simmitecan + 5-FU/LV regimen seemed to have a better efficacy. Nonetheless, the efficacy of this regimen needs to be further explored in the subsequent study.
西米替康是一种具有抗肿瘤活性的强效拓扑异构酶I抑制剂。本Ib期试验旨在研究西米替康单药或与其他药物联合使用的安全性和抗肿瘤效果。符合条件的晚期实体瘤患者没有进一步的标准治疗选择。患者被分配接受单药西米替康、西米替康联合5-氟尿嘧啶（5-FU）/亚叶酸钙（LV）或西米替康联合沙利度胺治疗，每2周为一个周期，直至疾病进展或出现不可接受的毒性。共入组41例患者，中位年龄55岁（范围29-69岁）。其中，13例患者接受西米替康单药治疗，10例接受西米替康+5-FU/LV治疗，18例接受西米替康+沙利度胺治疗。未发生剂量限制性毒性。总体而言，最常见的3/4级不良事件（AE）是中性粒细胞减少（西米替康、西米替康+5-FU/LV和西米替康+沙利度胺组分别为46.2%、70.0%和88.9%），与治疗相关的严重AE包括贫血和发热性中性粒细胞减少（西米替康组各为7.7%）、腹泻（西米替康+5-FU/LV组为10%）和发热性中性粒细胞减少（西米替康+沙利度胺组为5.6%）。大多数患者（24/41，58.3%）既往使用伊立替康治疗时病情进展；然而，1例接受西米替康+沙利度胺治疗的结直肠癌患者获得了部分缓解。西米替康、西米替康+5-FU/LV和西米替康+沙利度胺组的疾病控制率分别为46.2%、80.0%和61.1%。本研究表明，西米替康作为单药或联合治疗的一部分，其安全性可控。与单药西米替康相比，联合使用西米替康不存在任何安全问题。西米替康+5-FU/LV方案似乎疗效更好。尽管如此，该方案的疗效仍需在后续研究中进一步探索。
