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A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas.
Clinical Cancer Research (2009)
  • Miguel A. Villalona Calero, M.D.
Abstract
BACKGROUND:
Hepatocellular carcinoma (HCC) is on the rise worldwide. HCC responds poorly to chemotherapy. Lapatinib is an inhibitor of epidermal growth factor receptor and HER2/NEU both implicated in hepatocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in HCC.
METHODS:
A Fleming phase II design with a single stage of 25 patients with a 90% power to exclude a true response rate of <10% and detect a true response rate of > or =30% was used. The dose of lapatinib was 1,500 mg/day administered orally in 28-day cycles. Tumor and blood specimens were analyzed for expression of HER2/NEU/CEP17 and status of downstream signal pathway proteins.
RESULTS:
Twenty-six patients with HCC enrolled on this study. Nineteen percent had one prior therapy. Most common toxicities were diarrhea (73%), nausea (54%), and rash (42%). No objective responses were observed. Ten (40%) patients had stable disease as their best response including six (23%) with stable disease lasting >120 days. Median progression-free survival was 1.9 months and median overall survival was 12.6 months. Patients who developed a rash had a borderline statistically significant longer survival. Tissue and blood specimens were available on >90% of patients. No somatic mutations in EGFR (exons 18-21) were found. In contrast to our previous findings, we did not find evidence of HER2/NEU somatic mutations. PTEN, P-AKT, and P70S6K expression did not correlate with survival.
CONCLUSIONS:
Lapatinib is well-tolerated but seems to benefit only a subgroup of patients for whom predictive molecular or clinical characteristics are not yet fully defined.
Publication Date
September 15, 2009
Citation Information
Miguel A. Villalona Calero. "A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas." Clinical Cancer Research Vol. 15 Iss. 18 (2009) p. 5895 - 5901
Available at: http://works.bepress.com/miguel-villalonacalero/56/