Impact of Diabetes on Outcomes of Sorafenib Therapy for Hepatocellular Carcinoma

Costanzo, Giovan Giuseppe Di; Tortora, Raffaella; Morisco, Filomena; Addario, Luigi; Guarino, Maria; Cordone, G; Falco, Luigia De; Caporaso, N.

doi:10.1007/s11523-016-0454-5

Cited by 21 publications

(41 citation statements)

References 43 publications

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“…These findings were supported by recent meta-analyses, particularly for patients with HCC after potentially curative approaches [11,15,16]. The impact of diabetes mellitus on the outcome of patients with advanced HCC treated with sorafenib was recently evaluated in a large cohort study [41]. In accordance with our study, sorafenib was as effective in diabetic and non-diabetic patients (comparable median OS).…”

Section: Discussionsupporting

confidence: 90%

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

Labenz

Prenosil²,

Koch³

et al. 2017

Dig Dis

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Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

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Section: Discussionsupporting

confidence: 90%

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

Labenz

Prenosil²,

Koch³

et al. 2017

Dig Dis

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show abstract

“…However, in concert with the recent epidemic of obesity and metabolic syndrome in developed countries, the incidence and prevalence of non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) have also increased, and today they represent rapidly growing causes of end‐stage liver disease and HCC . Moreover, regardless of the aetiology of liver disease, metabolic disorders, such as obesity and diabetes, contribute to hepato‐cancerogenesis . Indeed, there are well established pathophysiological mechanisms linking obesity, diabetes and HCC .…”

Section: Introductionmentioning

confidence: 99%

Metabolic disorders across hepatocellular carcinoma in Italy

Morisco

Guarino

Valvano

et al. 2018

Liver International

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“…The safety and efficacy of sorafenib in HCC patients with diabetes was confirmed by Di Constanzo et al81 They found a comparable frequency of main AEs in both diabetes and nondiabetes groups, with the exception of rash, which was more frequent among diabetes patients (27.5% vs 17.6%, p =0.047). The median overall survival was 9 months in non-diabetes and 10 months in the diabetes group ( p =0.535) 81.…”

Section: Molecular Targeted Therapymentioning

confidence: 70%

Section: Molecular Targeted Therapymentioning

confidence: 97%

“…The median overall survival was 9 months in non-diabetes and 10 months in the diabetes group ( p =0.535) 81. Median time to progression was longer in diabetes than in the nondiabetes group ( p =0.038), suggesting a better anticancer effect of sorafenib in patients with diabetes 81. However, the concomitant use of sorafenib and metformin was associated with shorter median progression-free survival compared to patients receiving sorafenib alone (2.6 vs 5.0 months, p =0.029) 82.…”

Section: Molecular Targeted Therapymentioning

confidence: 98%

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Targeted therapy and personalized medicine in hepatocellular carcinoma: drug resistance, mechanisms, and treatment strategies

Galun

Srdiċ-Rajiċ²,

Bogdanović

et al. 2017

JHC

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Hepatocellular carcinoma (HCC) is characterized by a growing number of new cases diagnosed each year that is nearly equal to the number of deaths from this cancer. In a majority of the cases, HCC is associated with the underlying chronic liver disease, and it is diagnosed in advanced stage of disease when curative treatment options are not applicable. Sorafenib is a treatment of choice for patients with performance status 1 or 2 and/or macrovascular invasion or extrahepatic spread, and regorafenib is the only systemic treatment found to provide survival benefit in HCC patients progressing on sorafenib treatment. Other drugs tested in different trials failed to demonstrate any benefit. Disappointing results of numerous trials testing the efficacy of various drugs indicate that HCC has low sensitivity to chemotherapy that is in great part caused by multidrug resistance. Immunotherapy for HCC is a new challenging treatment option and involves immune checkpoint inhibitors/antibody-based therapy and peptide-based vaccines. Another challenging approach is microRNA-based therapy that involves two strategies. The first aims to inhibit oncogenic miRNAs by using miRNA antagonists and the second strategy is miRNA replacement, which involves the reintroduction of a tumor-suppressor miRNA mimetic to restore a loss of function.

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Impact of Diabetes on Outcomes of Sorafenib Therapy for Hepatocellular Carcinoma

Abstract: Sorafenib was as safe as effective in DIAB and in nDIAB patients. The longer TTP observed among DIAB than in nDIAB patients might suggest a better anticancer effect of sorafenib in patients with diabetes.

Cited by 21 publications

References 43 publications

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

Metabolic disorders across hepatocellular carcinoma in Italy

Targeted therapy and personalized medicine in hepatocellular carcinoma: drug resistance, mechanisms, and treatment strategies

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