Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma

PLoS One. 2014 Mar 10;9(3):e90909. doi: 10.1371/journal.pone.0090909. eCollection 2014.

Abstract

Background: The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.

Methods: Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS).

Results: Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively.

Conclusions: This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib.

Trial registration: ClinicalTrials.gov NCT00712790.

Publication types

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

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / physiopathology
  • Carcinoma, Hepatocellular / radiotherapy*
  • Carcinoma, Hepatocellular / surgery
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Embolization, Therapeutic / adverse effects
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / physiopathology
  • Liver Neoplasms / radiotherapy*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use*
  • Quality of Life
  • Sorafenib
  • Time Factors
  • Yttrium Radioisotopes / therapeutic use

Substances

  • Phenylurea Compounds
  • Yttrium Radioisotopes
  • Niacinamide
  • Sorafenib

Associated data

  • ClinicalTrials.gov/NCT00712790

Grants and funding

This study is funded jointly by the National Medical Research Council Singapore grant number NMRC/1161/2008 (http://www.nmrc.gov.sg/); Sirtex Medical Limited, Sydney, Australia; and Bayer Schering Pharma AG, Berlin, Germany, in the form of free therapeutics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.