Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study.
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
Pfizer Oncology.
Faivre
Sandrine
S
Beaujon University Hospital, Clichy, France. sandrine.faivre@bjn.aphp.fr
Raymond
Eric
E
Boucher
Eveline
E
Douillard
Jean
J
Lim
Ho Y
HY
Kim
Jun S
JS
Zappa
Magaly
M
Lanzalone
Silvana
S
Lin
Xun
X
Deprimo
Samuel
S
Harmon
Charles
C
Ruiz-Garcia
Ana
A
Lechuga
Maria J
MJ
Cheng
Ann Lii
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib