Stemmer Salomon M, Manojlovic Nebojsa S, Marinca Mihai Vasile, Petrov Petar, Cherciu Nelly, Ganea Doina, Ciuleanu Tudor Eliade, Pusca Ioana Adriana, Beg Muhammad Shaalan, Purcell William T, Croitoru Adina-Emilia, Ilieva Rumyana Nedyalkova, Natošević Sladjana, Nita Amedeia Lavinir, Kalev Dimitar Nikolaev, Harpaz Zivit, Farbstein Motti, Silverman Michael H, Bristol David, Itzhak Inbal, Fishman Pnina
Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv 49100, Israel.
Department of Gastroenterology and Hepatology, Military Medical Academy, 11000 Belgrade, Serbia.
Cancers (Basel). 2021 Jan 7;13(2):187. doi: 10.3390/cancers13020187.
Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child-Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; = 50) or placebo ( = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49-1.38; = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45-1.43, = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51-1.55, = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
在一项I/II期临床研究中，A3腺苷受体激动剂那莫德森在晚期肝细胞癌（HCC）和中度肝功能不全（Child-Pugh B级；CPB）患者中显示出了有前景的结果。这项II期研究调查了那莫德森作为此类患者二线治疗的效果。患者按2:1随机分组，分别接受每日两次（BID）的那莫德森（25毫克；n = 50）或安慰剂（n = 28）治疗。主要终点（总生存期[OS]）未达到。那莫德森/安慰剂组的中位OS分别为4.1/4.3个月（风险比[HR]，0.82；95%置信区间[CI] 0.49 - 1.38；P = 0.46）。对CPB7患者（34例接受那莫德森治疗，22例接受安慰剂治疗）进行的预先计划亚组分析显示，OS/无进展生存期（PFS）有非显著改善。OS：6.9个月对4.3个月；HR，0.81；95% CI：0.45 - 1.43，P = 0.46。PFS：3.5个月对1.9个月；HR，0.89；95% CI：0.51 - 1.55，P = 0.67（对数秩检验）。12个月OS的差异具有显著性（44%对18%，P = 0.028）。在基线后有≥1次评估的患者中确定了缓解率（34例接受那莫德森治疗，21例接受安慰剂治疗）。部分缓解分别在3/34（8.8%）和0/21（0%）的患者中实现。那莫德森耐受性良好，安全性与安慰剂组相当。未报告与治疗相关的死亡；无患者因毒性而退出。总之，那莫德森在HCC CPB患者中显示出了良好的安全性和初步疗效信号。
