Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma

Schmid, Irene; Häberle, Beate; Albert, Michael H.; Corbacioglu, Selim; Fröhlich, Birgit; Graf, Norbert; Kammer, Birgit; Kontny, Udo; Leuschner, Ivo; Scheel-Walter, Hans-Gerhard; Scheurlen, Wolfram; Werner, Sebastian; Wiesel, Thomas; Schweinitz, Dietrich von

doi:10.1002/pbc.23295

Cited by 75 publications

(55 citation statements)

References 18 publications

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“…Reconsidering the last two decades of clinical studies, with attempts to improve the outcome of patients suffering from advanced or recurrent pediatric HCC, a markedly increased event-free survival (EFS) or overall survival (OS) could not be achieved in any of the trials [4,5,7]. Since OS still remains poor with about 20%, it is of great interest to find alternative or additional therapy regimens that might improve these results.…”

Section: Discussionmentioning

confidence: 96%

“…The multikinase inhibitor sorafenib did not only exert positive results in terms of prolonged survival in adult carcinoma [13,14]; overall survival of children with pHCC treated with sorafenib in combination with cisplatin and doxorubicin was enhanced up to 50% in a pilot study of the German Pediatric Liver Tumor Group (GPOH) [7]. However, outcomes differed in these patients, presumably because of developing resistance.…”

Section: Discussionmentioning

confidence: 97%

“…In clinical trials of adult HCC, sorafenib alone or in combination with doxorubicin was only convincing as a palliative treatment approach [13,25]. The few existing data in children with pediatric HCC or Hepatoblastoma, with missing long-term results, suggest a similar impact of sorafenib on childhood liver tumors [7,26].…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, sorafenib also showed a high anti-tumoral activity in pediatric liver tumors like Hepatoblastoma in preclinical studies [15,16]. A pilot study considered sorafenib in combination with cisplatin and doxorubicin in pHCC [7]. The heterogenic response in this study with few cases demands a better understanding of the biological response of pHCC to sorafenib treatment.…”

Section: Introductionmentioning

confidence: 95%

“…Less than 20% of patients with advanced HCC exhibit a sustained survival. Therefore, alternative treatment strategies such as transarterial chemoembolization (TACE) or the use of kinase inhibitors were considered in pilot studies [6,7]. Other emerging molecular treatment approaches such as apoptosis sensitizers, therapeutic antibodies, and epigenetic agents may also possibly improve the outcome as observed for related tumors [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma

Nagel

Armeanu–Ebinger

Dewerth

et al. 2015

Experimental Cell Research

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma

Nagel

Armeanu–Ebinger

Dewerth

et al. 2015

Experimental Cell Research

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C/EBPβ enhances efficacy of sorafenib in hepatoblastoma

Pang

Miao

Zuo

et al. 2021

Cell Biology International

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Hepatoblastoma (HB) is the predominant hepatic neoplasm in infants and young children. Sorafenib has been used to treat adult and pediatric hepatocellular carcinoma. However, efficacy of monotherapy of sorafenib in HB is not sustained. In this study, we tested a possible combinatory therapy of sorafenib with the CCAAT/enhancer‐binding proteins (C/EBP) overexpression in HB cell line. Firstly, we evaluated the expression level of C/EBPβ in the patients with HB by analyzing The Cancer Genome Atlas data. Lower level of C/EBPβ was observed in tumor tissues in comparison with matched normal tissues. Next, we observed that combination of sorafenib and C/EBPβ overexpression led to dramatic growth and migration inhibition of live tumor cells which implied promising probability for clinical trial. Mechanistically, C/EBPβ which can be downregulated by Ras v12, augmented messenger RNA and protein levels of p53. These data suggested that a combination of sorafenib and C/EBPβ overexpression inhibited tumor growth synergistically and provided a promising approach to treat HB.

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Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study

Short

Kastenberg

Guo

et al. 2022

Cancer

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Background Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. Methods A multi‐institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB‐HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB‐HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α‐fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease‐free status at any point predicted survival. Conclusions This multi‐institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk‐stratified algorithms for children with HCC. Lay Summary This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

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Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma

Abstract: Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib.

Cited by 75 publications

References 18 publications

Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma

Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma

C/EBPβ enhances efficacy of sorafenib in hepatoblastoma

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study

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