Continuous sunitinib treatment in patients with advanced hepatocellular carcinoma: A swiss group for clinical cancer research (SAKK) and swiss association for the study of the liver (SASL) multicenter phase II trial (SAKK 77/06)

Dieter Koeberle, Michael Montemurro, Panagiotis Samaras, Pietro Majno, Mathew Simcock, Andreas Limacher, Stefanie Lerch, Kovàcs Katalin, Roman Inauen, Vivianne Hess, Piercarlo Saletti, Markus Borner, Arnaud Roth, G. Bodoky

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Background. Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). Patients and Methods. Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary end-point was progression-free survival at 12 weeks (PFS12). Results. Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. Conclusion. Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalOncologist
Volume15
Issue number3
DOIs
Publication statusPublished - 2010

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Multicenter Studies
Hepatocellular Carcinoma
Liver
Research
Neoplasms
Disease-Free Survival
Therapeutics
Liver Diseases
sunitinib
Protein-Tyrosine Kinases
Appointments and Schedules
Clinical Trials
Confidence Intervals
Neoplasm Metastasis
Survival
Pharmaceutical Preparations

Keywords

  • Hepatocellular carcinoma
  • RECIST
  • Sunitinib
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Continuous sunitinib treatment in patients with advanced hepatocellular carcinoma : A swiss group for clinical cancer research (SAKK) and swiss association for the study of the liver (SASL) multicenter phase II trial (SAKK 77/06). / Koeberle, Dieter; Montemurro, Michael; Samaras, Panagiotis; Majno, Pietro; Simcock, Mathew; Limacher, Andreas; Lerch, Stefanie; Katalin, Kovàcs; Inauen, Roman; Hess, Vivianne; Saletti, Piercarlo; Borner, Markus; Roth, Arnaud; Bodoky, G.

In: Oncologist, Vol. 15, No. 3, 2010, p. 285-292.

Research output: Contribution to journalArticle

Koeberle, Dieter ; Montemurro, Michael ; Samaras, Panagiotis ; Majno, Pietro ; Simcock, Mathew ; Limacher, Andreas ; Lerch, Stefanie ; Katalin, Kovàcs ; Inauen, Roman ; Hess, Vivianne ; Saletti, Piercarlo ; Borner, Markus ; Roth, Arnaud ; Bodoky, G. / Continuous sunitinib treatment in patients with advanced hepatocellular carcinoma : A swiss group for clinical cancer research (SAKK) and swiss association for the study of the liver (SASL) multicenter phase II trial (SAKK 77/06). In: Oncologist. 2010 ; Vol. 15, No. 3. pp. 285-292.
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abstract = "Background. Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). Patients and Methods. Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary end-point was progression-free survival at 12 weeks (PFS12). Results. Forty-five patients were enrolled. The median age was 63 years; 89{\%} had Child-Pugh class A disease and 47{\%} had distant metastases. PFS12 was rated successful in 15 patients (33{\%}; 95{\%} confidence interval, 20{\%}-47{\%}). Over the whole trial period, one complete response and a 40{\%} rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. Conclusion. Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).",
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AU - Koeberle, Dieter

AU - Montemurro, Michael

AU - Samaras, Panagiotis

AU - Majno, Pietro

AU - Simcock, Mathew

AU - Limacher, Andreas

AU - Lerch, Stefanie

AU - Katalin, Kovàcs

AU - Inauen, Roman

AU - Hess, Vivianne

AU - Saletti, Piercarlo

AU - Borner, Markus

AU - Roth, Arnaud

AU - Bodoky, G.

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N2 - Background. Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). Patients and Methods. Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary end-point was progression-free survival at 12 weeks (PFS12). Results. Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. Conclusion. Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

AB - Background. Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). Patients and Methods. Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary end-point was progression-free survival at 12 weeks (PFS12). Results. Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. Conclusion. Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

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KW - Tyrosine kinase inhibitor

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