Preventive effect of celecoxib in sorafenib-related hand-foot syndrome in hepatocellular carcinoma patients, a single-center, open-label, randomized, controlled clinical phase III trial

• Published in: American journal of cancer research Vol. 10; no. 5; pp. 1467 - 1476
• Main Authors: Chen, Jian-Cong, Wang, Jun-Cheng, Pan, Yang-Xun, Yi, Min-Jiang, Chen, Jin-Bin, Wang, Xiao-Hui, Fu, Yi-Zhen, Zhang, Yao-Jun, Xu, Li, Chen, Min-Shan, Zhang, Rong-Xin, Zhou, Zhong-Guo
• Format: Journal Article
• Language: English
• Published: e-Century Publishing Corporation 01.01.2020
• Subjects: Original
• ISSN: 2156-6976; 2156-6976

Skin toxicity, especially hand-foot syndrome (HFS), is one of the most common sorafenib-induced adverse events (AEs) in hepatocellular carcinoma (HCC) patients, leading to treatment interruption and failure. Mucocutaneous inflammation may cause HFS; therefore, we investigated whether celecoxib can alleviate HFS, improve patients’ quality of life and increase survival when administered in conjunction with active therapy. Our randomized, open-label study prospectively enrolled 116 advanced HCC patients receiving sorafenib as targeted therapy from July 2015 to July 2016. All patients were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib with or without celecoxib. Sorafenib-related AEs were recorded, Survival was compared between the two groups. Compared to the Sorafenib group, the SoraCele group had lower incidence rates of ≥ grade 2 and grade 3 HFS (63.8% vs 29.3%, P < 0.001; 19.0% vs 3.4%, P = 0.008, respectively), hair loss, rash and abdominal pain. Kaplan-Meier analysis revealed a lower risk of ≥ grade 2 HFS (HR, 0.384; P = 0.002) and a lower dose reduction/interruption rate (46.6% to 15.5%, P < 0.001) in the SoraCele group. Cox proportional hazards regression analysis demonstrated that celecoxib was the only independent predictive factor of developing ≥ grade 2 HFS (HR, 0.414; P = 0.004). Longer progression-free survival (PFS) was also observed in the SoraCele group ( P = 0.039), although overall survival was not prolonged ( P = 0.305). These results suggest that sorafenib + Celecoxib administration alleviated sorafenib-related skin toxicity. Longer PFS was achieved in clinical practice, although overall survival was not prolonged (ClinicalTrials.gov: NCT02961998).