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An exploratory clinical trial of apatinib combined with intensity-modulated radiation therapy for patients with unresectable hepatocellular carcinoma.

PURPOSE
To evaluate the clinical efficacy and safety of apatinib combined with intensity-modulated radiation therapy (IMRT) in patients with unresectable hepatocellular carcinoma (uHCC).


MATERIALS AND METHODS
Open-label, single-arm, exploratory clinical trial of apatinib combined with IMRT for uHCC patients. Patients aged 18-75 years with adequate hematological, liver, and renal functions and Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were enrolled in this study from March 2017 to September 2020. Patients were received IMRT (biological effective dose: 46-60 Gy) and continuous apatinib (250-500 mg/day) oral administration until HCC progression or unacceptable toxic effects. The endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety. The trial registration number is ChiCTR-OPC-17011890.


RESULTS
A total of 33 patients have taken part in the study. The median age was 58 years old (range 32-77), 27 (81.9%) patients were ECOG PS 0-1, and 28 (84.9%) patients were male. In addition, 25 (75.7%) patients suffered from hepatitis B, 32 cases (97.0%) were in Barcelona Clinic Liver Cancer (BCLC) Stages B-C, and eight (24.2%) had portal vein involvement. Moreover, 12 (36.4%) and 21 (63.6%) patients received apatinib as first-line and second or later-line therapy, respectively. The average follow-up was 11.4 months, the median PFS was 7.8 months (95% confidence interval: 3.9-11.7). The OS rates at 6 and 12 months were 96.7% and 66.2%. The ORR and DCR were 15.1% and 81.8%, respectively. Hepatic toxicity was the most common treatment-related adverse events in Grades 3-4 (12.1%). No radiation-induced liver disease and Grade 5 toxicity were recorded.


CONCLUSION
Apatinib combined with IMRT is a safe and effective method to improve PFS and DCR and has good anti-tumor activity in patients with uHCC.