Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation: A case-control study

Sposito, Carlo; Mariani, Luigi; Germini, Alessandro; Reyes, Maria Flores; Bongini, Marco; Grossi, G.; Bhoori, Sherrie; Mazzaferro, Vincenzo

doi:10.1016/j.jhep.2013.02.026

Cited by 127 publications

(144 citation statements)

References 24 publications

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“…This is consistent with a previous study by Wang et al (25), in which only grades 1 and 2 drug-related adverse events were observed with sorafenib therapy, as well as other studies that observed no serious adverse events associated with sorafenib therapy in patients with advanced HCC (48,64). By contrast, grade 4 liver-related adverse events have been reported for Child-Pugh class B patients (65), with poorer outcomes observed in class B versus class A advanced HCC patients following sorafenib therapy (66).…”

Section: Univariate Analysissupporting

confidence: 93%

“…Nagano et al noticed that the overall median progression-free survival (PFS) of advanced HCC was 2.0 months (40). In addition, the association between sorafenib therapy and longer DFS is largely concordant with previous studies in patients with HCC (25,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). In a pilot study by Wang et al (25) that included 31 patients at a high risk of recurrence, sorafenib therapy following hepatic resection significantly improved the time to recurrence as well as the recurrence rate.…”

Section: Discussionsupporting

confidence: 62%

“…In a different study, a complete response was observed in a single patient with hepatitis C virus-mediated cirrhosis and recurrent HCC with PVTT following treatment with 400 mg sorafenib once daily (42). Furthermore, in a case-controlled study of 39 patients that experienced HCC recurrence following liver transplantation, the median survival time from recurrence was significantly improved with sorafenib as compared with BSC, and sorafenib was identified as the only factor associated with survival by multivariate analysis (48). The effect of sorafenib on recurrence has also been observed in animal studies.…”

Section: Discussionmentioning

confidence: 94%

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Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

Liao

Zheng

et al. 2016

Oncology Letters

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Abstract. Sorafenib is the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC); however, its therapeutic value in patients with HCC following resection remains controversial. The current retrospective study was undertaken to assess the effects of sorafenib treatment following surgical resection in patients with advanced HCC disease who were at a high risk for recurrence. Between July 2010 and July 2013, a consecutive cohort of 42 patients with advanced HCC and at a high risk of recurrence (i.e., those with portal vein tumor thrombosis, adjacent organ involvement or tumor rupture) who underwent resection were analyzed. The patients were categorized into the sorafenib group (n=14) or the best supportive care (BSC) group (n=28). Although the histological grade, Barcelona Clinic Liver Cancer Stage, tumor size, nodule number and proportion of patients with high serum α-fetoprotein levels were comparable between the sorafenib and BSC groups, those receiving sorafenib following resection had significantly longer disease-free survival (DFS) of 5.2 months [95% confidence interval (CI), 1.2-9.2 months] compared with the BSC group [1.8 months (95% CI, 0.6-3.0 months)]. No differences in overall survival were noted between the groups. Furthermore, no drug-related adverse events resulted in discontinuation of sorafenib therapy. Univariate log-rank analysis revealed that sorafenib treatment (P=0.002) and treatment prior to resection (P=0.012) were significantly associated with longer DFS; however, sorafenib therapy (P= 0.027) and tumor size (P= 0.028) were associated with longer DFS by multivariate analysis. Furthermore, sorafenib was well-tolerated and improved DFS in patients with advanced HCC who underwent hepatic resection. Thus, tumor resection followed by sorafenib therapy may represent an effective therapeutic strategy for patients with advanced HCC. This possibility should be confirmed in larger, multicenter studies.

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Section: Univariate Analysissupporting

confidence: 93%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 94%

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Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

Liao

Zheng

et al. 2016

Oncology Letters

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“…Typically the combination of sorafenib and mTOR inhibitors has been preferred, as mTOR inhibition has the strongest evidence and rationale for an anticancer effect. However, sorafenib is poorly tolerated in liver transplant patients, with or without mTOR immunosuppression, making it difficult to achieve a therapeutic dose of sorafenib (84)(85)(86)(87). Nonetheless, there are a couple of case series that have described a survival benefit from using adjuvant sorafenib in post-transplant patients at high risk of recurrence (88)(89)(90).…”

Section: Immunosuppression and Sorafenibmentioning

confidence: 99%

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence

Khorsandi¹,

Heaton²

2016

Transl. Gastroenterol. Hepatol.

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“…Compared to various therapeutic approaches used before recurrence, including local treatment, hepatic resection and chemotherapy, no standard posttransplant adjuvant chemotherapy has been established. Sorafinib (SORA) and everolimus (EVL) have already been investigated for application in recurrence HCC after LT [3][4][5][6] based on roles of B-Raf and mammalian target of rapamycin (mTOR)/protein kinase B (AKT) pathways in the pathogenesis of HCC [7,8]. Targeted next generation sequencing (NGS) of tumor samples can provide molecular abnormalities of different pathways for prediction of treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

Oxaliplatin Plus S1 for Treating Sorafenib-Refractory Recurrent Hepatocellular Carcinoma after Liver Transplantation

Sun¹,

Cai²,

Li³

et al. 2017

J Carcinog Mutagen

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Recurrent hepatocellular carcinoma (HCC) following liver transplantation (LT) correlates with a poor prognosis due to the lack of effective therapeutic approaches after sorafenib (SORA) or everolimus (EVL) resistance. We assessed the efficacy of SOX (S-1 and oxaplatin) after failed SORA for HCC recurrence after LT based on the results of next generation sequences (NGS). A patient with HCC recurrence after LT was treated with SORA until severe side effect. And then NGS was performed on the primary and metastatic tumor tissues. Investigations on molecular aberrations in cellular pathways and SNPs of drug-related genes were applied. The result of the first NGS shows the benefit from platinum drugs and no abnormalities in PI3K/AKT/mTOR pathway. He received SOX regimen for 4 cycles with progression-free survival (PFS) as long as 4.3 months. NGS of lung and liver metastasis tissues after disease progression still did not match molecular target of everolimus, which he switched to for experimental therapy. He died of failure treatment with 17.3 months overall survival. SOX regimen may benefit recurrent HCC after LT. NGS may provide personalized clinical care for HCC patients.

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Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation: A case-control study

Cited by 127 publications

References 24 publications

Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence

Optimization of immunosuppressive medication upon liver transplantation against HCC recurrence

Oxaliplatin Plus S1 for Treating Sorafenib-Refractory Recurrent Hepatocellular Carcinoma after Liver Transplantation

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