Is intra-patient sorafenib dose re-escalation safe and tolerable in patients with advanced hepatocellular carcinoma?

Background: Although sorafenib improves survival in patients with hepatocellular carcinoma (HCC), doses have to be reduced in quite a few patients because of adverse events. We investigated whether intra-patient sorafenib dose re-escalations were safe and tolerable in patients with advanced HCC.

Methods: Of the 73 advanced HCC patients treated with sorafenib, 42 achieved a tolerable dose with a dose reduction. We evaluated safety and tolerability in patients who attempted intra-patient dose re-escalations from the reduced dose.

Results: Thirteen of 42 patients increased the sorafenib dose from the reduced dose. Ten patients had a tolerable dose of 400 mg on alternate days, and 3 patients had a tolerable dose of 400 mg daily. Dose-limiting toxicity (DLT), defined as toxicity resulting in a dose reduction, was observed in 8 of 13 patients as a hand-foot skin reaction (HFSR), and DLT was noted in 2 of 13 patients as an increase in alanine aminotransferase/aspartate aminotransferase levels. Seven of 13 patients did not exhibit DLT after dose re-escalations. Although 6 patients exhibited DLT, the cause of the adverse event was HFSR in all cases. The median escalation dose ratio, which was calculated as the ratio of the real cumulative dose to the cumulative dose when continued at the tolerable dose after dose re-escalation, was 1.84.

Conclusions: The results of the present study indicated that intra-patient sorafenib dose re-escalations were safe and tolerable. Further prospective analyses are needed to determine in more detail the safety and efficacy of intra-patient sorafenib dose re-escalations.