To investigate the clinical efficacy and safety of sorafenib sequential regorafenib in the treatment of recurrence of hepatocellular carcinoma after liver transplantation.

The clinical data of 14 patients with hepatocellular carcinoma who had tumor recurrence after liver transplantation and received sorafenib and regorafenib were collected from the Affiliated Hospital of Qingdao University from February 2014 to September 2020. After the clinical diagnosis of recurrence of liver cancer, sorafenib (400 mg/time, twice a day, oral) was added for treatment. When the disease progressed or the adverse events of sorafenib was not tolerated, sequentially treated with regorafenib (160 mg/time, once a day, oral, continuous medication for 21 days, stop medication for 7 days, every 28 days is a cycle) treatment. The medication was supplemented with symptomatic support treatment, followed up regularly, alpha-fetoprotein (AFP), liver function, immunosuppressive blood concentration, ultrasound or CT and other imaging examinations were monitored, and adverse events were recorded.

Among the 14 patients who finally met the inclusion criteria, 12 were males and 2 were females; the median age was 56.5 (40.0-65.0) years. The median interval from tumor recurrence after liver transplantation to initiation of sorafenib was 1.0 (0.1-6.4) months. The median treatment time for sorafenib was 2.7 (0.9-9.2) months, and the median time to progression (mTTP) was 4.4 (0.9-14.1) months. The median time between cessation of sorafenib and initiation of regorafenib was 16.5 (1-366) d; the median treatment time of regorafenib was 9.3 (1.3-20.4) months, the mTTP was 2.8 (1.0-9.7) months, and the median overall survival (mOS) was 20.1 (95%CI 0.7-39.5) months. There were no significant differences in AFP and liver function indexes before and after sorafenib treatment (all P>0.05). AFP increased and serum albumin decreased after treatment, with statistical significance (all P<0.05). ALT, AST and total bilirubin changes had no statistical difference (all P>0.05). Adverse events during the treatment of sorafenib and regofinib included: diarrhea (9 cases and 10 cases), fatigue (9 cases and 6 cases), decreased body mass (3 cases and 2 cases), and hand-foot skin reactions (1 case and 2 cases), respectively. Among them, sorafenib treatment was terminated in 2 cases due to severe diarrhea, and the dosage of regogafenib was reduced in 1 case, and the treatment of regogafenib was discontinued in 1 case due to hand and foot skin reaction, respectively. The other patients had adverse reactions and were tolerated after symptomatic treatment. By September 2020, the median follow-up time was 12.4 (5.6-34.2) months, and a total of 7 patients died, all due to tumor progression after liver cancer recurrence. Of the 7 patients who survived, 3 were discontinued due to lung tumor progression, and 4 were continued with regofinib. The mOS was 14.4 (95%CI 3.4-25.4) months for 14 patients who received sorafenib sequential regolfinib, and the 1-year and 2-year cumulative survival rates were 67.7% and 48.4%, respectively.

Sorafenib sequential regorafenib for the treatment of tumor recurrence after liver transplantation of hepatocellular carcinoma has good clinical efficacy and safety, but a larger sample size of research support is still needed.