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

Sandrine Faivre, Eric Raymond, Eveline Boucher, Jean Douillard, Ho Y. Lim, Jun Suk Kim, Magaly Zappa, Silvana Lanzalone, Xun Lin, Samuel DePrimo, Charles Harmon, Ana Ruiz-Garcia, Maria J. Lechuga, Ann Lii Cheng

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Abstract

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.

Original languageEnglish
Pages (from-to)794-800
Number of pages7
JournalThe Lancet Oncology
Volume10
Issue number8
DOIs
Publication statusPublished - 2009 Aug 1

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Hepatocellular Carcinoma
Safety
Hand-Foot Syndrome
Asthenia
sunitinib
Neutropenia
Thrombocytopenia
Protein-Tyrosine Kinases
Anemia
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Oncology

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Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma : an open-label, multicentre, phase II study. / Faivre, Sandrine; Raymond, Eric; Boucher, Eveline; Douillard, Jean; Lim, Ho Y.; Kim, Jun Suk; Zappa, Magaly; Lanzalone, Silvana; Lin, Xun; DePrimo, Samuel; Harmon, Charles; Ruiz-Garcia, Ana; Lechuga, Maria J.; Cheng, Ann Lii.

In: The Lancet Oncology, Vol. 10, No. 8, 01.08.2009, p. 794-800.

Research output: Contribution to journalArticle

Faivre, S, Raymond, E, Boucher, E, Douillard, J, Lim, HY, Kim, JS, Zappa, M, Lanzalone, S, Lin, X, DePrimo, S, Harmon, C, Ruiz-Garcia, A, Lechuga, MJ & Cheng, AL 2009, 'Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study', The Lancet Oncology, vol. 10, no. 8, pp. 794-800. https://doi.org/10.1016/S1470-2045(09)70171-8
Faivre, Sandrine ; Raymond, Eric ; Boucher, Eveline ; Douillard, Jean ; Lim, Ho Y. ; Kim, Jun Suk ; Zappa, Magaly ; Lanzalone, Silvana ; Lin, Xun ; DePrimo, Samuel ; Harmon, Charles ; Ruiz-Garcia, Ana ; Lechuga, Maria J. ; Cheng, Ann Lii. / Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma : an open-label, multicentre, phase II study. In: The Lancet Oncology. 2009 ; Vol. 10, No. 8. pp. 794-800.
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abstract = "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.",
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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 Suk

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

PY - 2009/8/1

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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.

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