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


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.
Centre for Research on Angiogenesis Inhibitors, Department of Medical Oncology, Cochin Teaching Hospital, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. olivier.mir@cch.aphp.fr
Olivier
O
Mir
Romain
R
Coriat
Benoit
B
Blanchet
Jean-Philippe
JP
Durand
Pascaline
P
Boudou-Rouquette
Judith
J
Michels
Stanislas
S
Ropert
Michel
M
Vidal
Stanislas
S
Pol
Stanislas
S
Chaussade
François
F
Goldwasser
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies; D055948:Sarcopenia / Q000139:chemically induced*; D000077157:Sorafenib; D016019:Survival Analysis
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib