A phase II randomized dose escalation trial of sorafenib in patients with advanced hepatocellular carcinoma

Oncologist. 2013;18(4):379-80. doi: 10.1634/theoncologist.2012-0221. Epub 2013 Apr 11.

Abstract

Background: Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated.

Methods: Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to progression, overall survival, and safety were also evaluated.

Results: The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%).

Conclusions: Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials.

Trial registration: ClinicalTrials.gov NCT00490685.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Neoplasm Staging
  • Niacinamide / administration & dosage
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacokinetics
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacokinetics
  • Sorafenib

Substances

  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib

Associated data

  • ClinicalTrials.gov/NCT00490685