O'Neil BH, Goff LW, Kauh JS, Strosberg JR, Bekaii-Saab TS, Lee RM, Kazi A, Moore DT, Learoyd M, Lush RM, Sebti SM, Sullivan DM. "J Clin Oncol. 2011 Jun"
PURPOSE:
Hepatocellular carcinoma (HCC) is actually a typical and deadly malignancy with few systemic treatment options. The RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is activated in approximately 50% to 60% of HCCs and represents a possible target for treatment. Selumetinib is surely an orally offered inhibitor of MEK tyrosine kinase activity.
PATIENTS AND Techniques:
Patients with regionally superior or metastatic HCC who had not been treated with prior systemic therapy were enrolled on towards the research.
Sufferers had been handled with ARRY-142886 at its advised stage II dose of 100 mg two times each day continuously; Cycle length was 21 days; Imaging was carried out every two cycles; Biopsies had been acquired at baseline and at steady-state within a subset of patients, and pharmacokinetic (PK) analysis was carried out on all patients.
Final results Nineteen patients were enrolled, 17 of whom had been evaluable for response. Most (82%) had Child-Pugh A cirrhosis. Toxicity was in keeping with other scientific studies of selumetinib in noncirrhotic sufferers. PK parameters were also comparable to individuals in noncirrhotic individuals. No radiographic response was noticed within this group, and also the study was stopped in the interim analysis. Of 11 sufferers3 (27%) had decreases of 50% or more. Median time for you to progression was eight weeks. Inhibition of ERK phosphorylation was demonstrated by Western blotting.
CONCLUSION:
In this research of ARRY-142886 for sufferers with HCC, no radiographic responses had been observed and time for you to progression was short, which suggests minimal single-agent exercise regardless of proof of suppression of target activation.
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