期刊论文详细信息
Cancers
Namodenoson in Advanced Hepatocellular Carcinoma and Child–Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial
SalomonM. Stemmer1  NebojsaS. Manojlovic2  Petar Petrov3  RumyanaNedyalkova Ilieva4  MihaiVasile Marinca5  MuhammadShaalan Beg6  WilliamT. Purcell7  TudorEliade Ciuleanu8  Doina Ganea9  Nelly Cherciu1,10  AmedeiaLavinir Nita1,11  Adina-Emilia Croitoru1,12  IoanaAdriana Pusca1,13  DimitarNikolaev Kalev1,14  Sladjana Natošević1,15  Pnina Fishman1,16  David Bristol1,16  MichaelH. Silverman1,16  Motti Farbstein1,16  Inbal Itzhak1,16  Zivit Harpaz1,16 
[1] 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;Department of Medical Oncology and Oncological Diseases in Pneumology, Complex Oncology Center–Plovdiv, EOOD, 4000 Plovdiv, Bulgaria;Department of Medical Oncology, Multiprofile Hospital for Active Treatment Central Onco Hospital OOD, 4000 Plovdiv, Bulgaria;Department of Oncology, Iasi Regional Oncology Institute, Institutul Regional de Oncologie Iasi—Sectia Oncologie Medical, 700483 Iasi, Romania;Division of Hematology and Medical Oncology, the University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA;Institute of Oncology, University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania;Medical Oncology Department, Sf. Ioan Cel Nou County Clinical Emergency Hospital, 720224 Suceava, Romania;Oncology Department, Clinica Onco-Life, 200255 Craiova, Romania;Oncology Department, County Hospital Prahova, 100001 Ploiesti, Romania;Oncology Department, Fundeni Clinical Hospital, 022328 Bucharest, Romania;Oncology Department, S.C. Pelican Impex S.R., 410469 Oradea, Romania;Oncology Department, Sveta Marina University Hospital, 9002 Varna, Bulgaria;Oncology Department, Zdravstveni Centar Kladovo, 19320 Kladovo, Serbia;R&D, Can-Fite BioPharma, 10 Bareket St., P.O.Box 7537, Petah-Tikva 49170, Israel;
关键词: Child–Pugh B;    hepatocellular carcinoma;    namodenoson;    overall survival;    randomized clinical trial;   
DOI  :  10.3390/cancers13020187
来源: DOAJ
【 摘 要 】

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; n = 50) or placebo (n = 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; p = 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, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 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.

【 授权许可】

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