Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;7(5):e37563.
doi: 10.1371/journal.pone.0037563. Epub 2012 May 30.

Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma

Olivier Mir  1 , Romain Coriat, Benoit Blanchet, Jean-Philippe Durand, Pascaline Boudou-Rouquette, Judith Michels, Stanislas Ropert, Michel Vidal, Stanislas Pol, Stanislas Chaussade, François Goldwasser
Affiliations

Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma

Olivier Mir et al. PLoS One. 2012.

Abstract

Background: Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients.

Patients and methods: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans.

Results: Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013).

Conclusions: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: Prof. Goldwasser and Dr. Ropert have acted as paid consultants for Bayer Healthcare. Dr. Mir and Dr. Coriat have acted as paid consultants for Roche. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. The other authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1. Study timelines.
Figure 2
Figure 2. Patients selection for the present study.
Figure 3
Figure 3. Prevalence of dose-limiting toxicities and estimated sorafenib AUC in sarcopenic and non-sarcopenic patients.
Figure 4
Figure 4. Progression-free and overall survival in sarcopenic (dot line) and non-sarcopenic (solid line) HCC patients receiving sorafenib.
See this image and copyright information in PMC

References

    1. Jemal A, Bray F Center MM, Ferlay J, Ward E, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90. - PubMed
    1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–1917. - PubMed
    1. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–844. - PubMed
    1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390. - PubMed
    1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39:412–423. - PMC - PubMed

MeSH terms