Gordon SW, et al. - In patients with unresectable hepatocellular carcinoma, researchers initiated a phase I study to determine the recommended phase 2 dose of sorafenib in combination with vorinostat. For this investigation, study participants received vorinostat (200 to 400 mg by mouth once daily, 5 of 7 d) and sorafenib at standard or reduced doses (400 mg [cohort A] or 200 mg [cohort B] by mouth twice daily). Dose-limiting toxicity was assessable in patients receiving 14 days of vorinostat in cycle 1. In this analysis, 16 patients were treated and 13 patients were evaluable for response. While some patients had long-lasting disease control, in most patients, the addition of vorinostat to sorafenib led to toxicity (hypokalemia, maculopapular rash, hepatic failure, hypophosphatemia, thrombocytopenia), requiring dose modifications that prevented the recommended phase 2 dose from being determined. For further exploration with this vorinostat schedule, the combination is not recommended in this patient population.