Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma.
<h4>Background</h4>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.<h4>Patients and methods</h4>The charac...
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2012
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oai:doaj.org-article:b575cc75d589484f80a9f59965af3ec22021-11-18T07:16:58ZSarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma.1932-620310.1371/journal.pone.0037563https://doaj.org/article/b575cc75d589484f80a9f59965af3ec22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22666367/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.Olivier MirRomain CoriatBenoit BlanchetJean-Philippe DurandPascaline Boudou-RouquetteJudith MichelsStanislas RopertMichel VidalStanislas PolStanislas ChaussadeFrançois GoldwasserPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37563 (2012) |
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Medicine R Science Q Olivier Mir Romain Coriat Benoit Blanchet Jean-Philippe Durand Pascaline Boudou-Rouquette Judith Michels Stanislas Ropert Michel Vidal Stanislas Pol Stanislas Chaussade François Goldwasser Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| description |
<h4>Background</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment. |
| format |
article |
| author |
Olivier Mir Romain Coriat Benoit Blanchet Jean-Philippe Durand Pascaline Boudou-Rouquette Judith Michels Stanislas Ropert Michel Vidal Stanislas Pol Stanislas Chaussade François Goldwasser |
| author_facet |
Olivier Mir Romain Coriat Benoit Blanchet Jean-Philippe Durand Pascaline Boudou-Rouquette Judith Michels Stanislas Ropert Michel Vidal Stanislas Pol Stanislas Chaussade François Goldwasser |
| author_sort |
Olivier Mir |
| title |
Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| title_short |
Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| title_full |
Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| title_fullStr |
Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| title_full_unstemmed |
Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| title_sort |
sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/b575cc75d589484f80a9f59965af3ec2 |
| work_keys_str_mv |
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