Functional and Clinical Evidence of the Influence of Sorafenib Binding to Albumin on Sorafenib Disposition in Adult Cancer Patients

Tod, Michel; Mir, Olivier; Bancelin, N.; Coriat, Romain; Thomas-Schoemann, Audrey; Taieb, F.; Boudou‐Rouquette, Pascaline; Ropert, Stanislas; Michels, Judith; Abbas, Halim; Durand, J.; Dauphin, A.; Vidal, Michel; Goldwasser, François; Blanchet, Benoı̂t

doi:10.1007/s11095-011-0499-1

Cited by 36 publications

(19 citation statements)

References 26 publications

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“…Few studies evaluated the prognostic value of 18 F-fluorodeoxyglucose-PET (18-FDG-PET) in patients receiving antiangiogenic agents for advanced HCC [157,158] . In a small cohort study, Lee et al [159] found that the degree of FGD uptake correlates with outcome in Korean patients with advanced HCC treated with sorafenib.…”

Section: F-fluorodeoxyglucos-petmentioning

confidence: 99%

“…Undeniably, such findings should be verified by prospective evaluation in large cohort patients. Finally, no data are/is available regarding the prognostic or predictive value of 18 F-fluorocholine, a PET tracer of lipid metabolism, that is supposed to be more sensitive than 18 F-FDG for HCC detection [158] , in patients receiving antiangiogenic drugs for HCC.…”

Section: F-fluorodeoxyglucos-petmentioning

confidence: 99%

“…In some emerging countries, the drug is not even approved for patients with advanced HCC. Otherwise, published data and clinical practice highlight a great inter-individual and even intra-individual variation regarding clinical benefit and toxicity [17][18][19][20][21][22] . For clinicians, there is an unmet need to identify patients more likely to benefit from treatment.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

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Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

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Section: F-fluorodeoxyglucos-petmentioning

confidence: 99%

Section: F-fluorodeoxyglucos-petmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Bouattour

Payancé

Wassermann

2015

WJH

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“…Sorafenib is known to bind to albumin resulting in a strong effect on sorafenib clearance in albumine mia and therefore on its disposition in adult cancer patients with advanced solid tumors (17,18). In several pathological states, endogenous ligands may accumulate to relatively high concentrations able to displace drugs highly bound to albumin, resulting in a significant increase in the unbound fraction of drugs (22).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, variations in sorafenib binding may contribute to the variability in sorafenib exposure. A recent study reported the characterization of in vitro sorafenib binding properties to albumin and the effect of albuminemia on sorafenib clearance and its disposition in cancer patients (17). Similar reports have shown that sorafenib is highly protein-bound in human plasma with a higher affinity towards albumin and that limited free drugs may play a role in its borderline clinical activity (18).…”

Section: Introductionmentioning

confidence: 89%

Exogenous albumin inhibits sorafenib-induced cytotoxicity in human cancer cell lines

Kanno

Itoh

Suzuki

et al. 2012

Molecular and Clinical Oncology

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Abstract. Sorafenib is an orally administered multikinase inhibitor that exhibits anti-angiogenic and anti-tumor activity. Sorafenib is also known to bind to protein (>99.5%), suggesting protein binding may be involved in sorafenib pharmacokinetic variability. Albumin is a major drug-binding protein. In this study, we examined the effect of albumin on sorafenib-induced cytotoxicity using two in vitro culture cell lines, human hepatoma Huh-7 cells and androgen-independent prostate cancer PC-3 cells. The cells were cultured and incubated, and cytotoxicity was assessed. Results were confirmed by western blotting. The presence of exogenous albumin markedly blocked the sorafenib-induced cytotoxicity in the two cell lines. Albumin concentration, the change of pharmacological signal transduction as Raf-B, vascular endothelial growth factor (VEGF), and phosphorylation of MEK1/2 or ERK1/2 were found to be decreased by sorafenib. Co-incubation of warfarin, a representative coumarin anticoagulant and potent binding activity, with albumin enhanced the cytotoxic effects by sorafenib. These mechanisms depend on the high binding proper ties of sorafenib and exogenous albumin. Furthermore, we investigated the effects of endo genous albumin expression on sorafenib-induced cytotoxicity using the siRNA knockdown system or transfected expression vector assay. However, the cytotoxic effects by sorafenib showed little change either with the knockdown or overexpression of albumin. Our results suggest that particular care should be taken with albuminemia or the combined use of drugs with a high affinity for albumin, such as warfarin, and sorafenib in the treatment of cancer patients. Our findings may be useful to the cancer therapeutic strategy by sorafenib. IntroductionAlbumin is the most abundant plasma protein synthesized primarily by liver cells. It is important in regulating blood volume by maintaining the oncotic pressure and also serving as a carrier for various molecules of low water solubility and transport drugs. This highly soluble protein is present in human plasma at a normal concentration between 35 and 50 g/l (1). The half-life of albumin is approximately 19 days and accounts for at least 10% of liver protein synthesis. This suggests that 10-15 g of albumin is produced per day in healthy subjects (2). Serum albumin concentrations below the normal range occur in a variety of disorders. Among these disorders are those associated with malnutrition and malabsorption, where protein is either not consumed in the diet or is lost through the gastrointestinal tract (3). Subsequently, a decrease in albumin concentration is frequently observed in patients with liver disorders (4), and plasma albumin is also reduced in cancer (5) and sepsis (6). Specifically, in nephrotic syndrome or protein-losing gastroenteropathy, plasma albumin is highly reduced to <20 g/l due to excessive albumin loss in urine or incomplete albumin synthesis (7). Thus, lower serum albumin (i.e., hypoalbuminaemia) is likely to be affected by a higher binding aff...

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Optimisation thérapeutique par la gestion des toxicités : expérience du Centre d’Étude et de Recours sur les Inhibiteurs de l’Angiogenèse (CERIA)

Boudou‐Rouquette¹,

Goldwasser²

2013

Médecine Personnalisée en Cancérologie Digestive

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Functional and Clinical Evidence of the Influence of Sorafenib Binding to Albumin on Sorafenib Disposition in Adult Cancer Patients

Abstract: These findings highlight the major influence of albuminemia on sorafenib clearance and its disposition in cancer patients.

Cited by 36 publications

References 26 publications

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

Exogenous albumin inhibits sorafenib-induced cytotoxicity in human cancer cell lines

Optimisation thérapeutique par la gestion des toxicités : expérience du Centre d’Étude et de Recours sur les Inhibiteurs de l’Angiogenèse (CERIA)

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