Sorafenib dose escalation in the treatment of advanced hepatocellular carcinoma

Although sorafenib has shown survival benefits in patients with hepatocellular carcinoma (HCC), many patients require discontinuation or dose reduction due to adverse events (AEs). We applied a dose escalation scheme to increase patient compliance and avoid AEs.

Of 267 HCC patients treated with first-line sorafenib, 25 at increased risk of AEs, including those with advanced liver cirrhosis, a history of liver transplantation, or cytopenia, received the dose escalation scheme. They started on a reduced dose of sorafenib which increased to the standard dosage according to tolerance in each patient. We analyzed the efficacy and safety of the dose escalation scheme.

Patients with risk factors showed a lower disease control rate, shorter survival, and more frequently grade 3/4 AEs. Among patients presenting risk factors, the dose scheme did not affect the efficacy of sorafenib or survival, but reduced the incidence of grade 3/4 AEs. Rates of sorafenib discontinuation and dose reduction related to AEs were also lower in the dose escalation group. Dose escalation to the standard dose of sorafenib was achieved in 16 of the 25 patients in the dose escalation group (64.0%). After 2 weeks, the dose intensity of sorafenib did not differ between the two dose schemes.

The sorafenib dose escalation scheme may increase patient compliance and tolerance to prolonged treatment, thus enhancing the efficacy of sorafenib in patients at high risk of AEs or with poor tolerance. Further prospective analyses are needed to determine the usefulness of the dose escalation scheme.