TY - JOUR
T1 - Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma
T2 - an open-label, multicentre, phase II study
AU - Faivre, Sandrine
AU - Raymond, Eric
AU - Boucher, Eveline
AU - Douillard, Jean
AU - Lim, Ho Y.
AU - Kim, Jun S.
AU - Zappa, Magaly
AU - Lanzalone, Silvana
AU - Lin, Xun
AU - DePrimo, Samuel
AU - Harmon, Charles
AU - Ruiz-Garcia, Ana
AU - Lechuga, Maria J.
AU - Cheng, Ann Lii
N1 - Funding Information:
SF, ER, JD, and ALC have been compensated as consultants and advisers to Pfizer Inc. SF, ER, and ALC have received research funding from Pfizer Inc. SL, XL, CH, AR-G, and MJL are employees of Pfizer Oncology. SL, XL, SD, a close family member of CH, and MJL, own stock in Pfizer Inc. ALC has received honoraria from Pfizer Inc. EB, HYL, JSK, and MZ declared no conflicts of interest.
Funding Information:
The study was sponsored by Pfizer Oncology. Editorial assistance was provided by Christine Arris (ACUMED), funded by Pfizer Oncology. We thank S Pitman-Lowenthal for medical expertise. We also acknowledge L Sherman and K Letrent for their input into the study and their comments on the manuscript.
PY - 2009/8
Y1 - 2009/8
N2 - Background: Hepatocellular carcinoma (HCC) tumour spread is partly dependent on neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties, was assessed in patients with advanced unresectable HCC. Methods: Between February and July, 2006, eligible patients were enrolled and treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment). The primary endpoint of this Simon two-stage phase II trial was objective response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with an expected response rate of 15%. This trial is registered with ClinicalTrials.gov, number NCT00247676. Findings: Of 37 patients enrolled, one (2·7%) patient experienced a confirmed partial response, giving an overall objective response rate of 2·7% (95% CI 0·1-14·2); on the basis of this, the trial did not proceed to the second stage. 13 (35%) of 37 patients achieved stable disease for over 3 months. Commonly observed grade 3 and 4 adverse events included thrombocytopenia (14 of 37; 37·8%), neutropenia (nine of 37; 24·3%), asthenia (five of 37; 13·5%), hand-foot syndrome (four of 37; 10·8%), and anaemia (four of 37; 10·8%). There were four deaths among the 37 patients (10·8%) that were possibly related to treatment. Interpretation: Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC. The response rate was low, and the study did not meet the primary endpoint based on RECIST criteria. Funding: Pfizer Oncology.
AB - Background: Hepatocellular carcinoma (HCC) tumour spread is partly dependent on neoangiogenesis. In this open-label, multicentre, phase II trial done in Europe and Asia, sunitinib, a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties, was assessed in patients with advanced unresectable HCC. Methods: Between February and July, 2006, eligible patients were enrolled and treated with repeated cycles of oral sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off treatment). The primary endpoint of this Simon two-stage phase II trial was objective response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with an expected response rate of 15%. This trial is registered with ClinicalTrials.gov, number NCT00247676. Findings: Of 37 patients enrolled, one (2·7%) patient experienced a confirmed partial response, giving an overall objective response rate of 2·7% (95% CI 0·1-14·2); on the basis of this, the trial did not proceed to the second stage. 13 (35%) of 37 patients achieved stable disease for over 3 months. Commonly observed grade 3 and 4 adverse events included thrombocytopenia (14 of 37; 37·8%), neutropenia (nine of 37; 24·3%), asthenia (five of 37; 13·5%), hand-foot syndrome (four of 37; 10·8%), and anaemia (four of 37; 10·8%). There were four deaths among the 37 patients (10·8%) that were possibly related to treatment. Interpretation: Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC. The response rate was low, and the study did not meet the primary endpoint based on RECIST criteria. Funding: Pfizer Oncology.
UR - http://www.scopus.com/inward/record.url?scp=67651165187&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(09)70171-8
DO - 10.1016/S1470-2045(09)70171-8
M3 - Article
C2 - 19586800
AN - SCOPUS:67651165187
VL - 10
SP - 794
EP - 800
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 8
ER -