New agents on the horizon in hepatocellular carcinoma

Zhu, Andrew X.

doi:10.1177/1758834012458480

Cited by 19 publications

(21 citation statements)

References 46 publications

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“…Other systemic therapy drugs such as doxorubicin, cisplatin, and 5-FU have been used for the treatment of HCC but with no evidence of improved survival [44,45], probably due to HCC resistance to these therapies [15], their increased toxicity counteracting the benefit [45,46], and the surrogate endpoints used to predict survival [47,48].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of the FOLFOX4 Regimen Versus Doxorubicin in Chinese Patients With Advanced Hepatocellular Carcinoma: A Subgroup Analysis of the EACH Study

et al. 2014

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Background. The EACH study assessed the efficacy of oxaliplatin, 5-fluorouracil, and leucovorin (the FOLFOX4 regimen) compared with doxorubicin alone in terms of overall survival (OS), progression-free survival (PFS), and safety in patients with advanced hepatocellular carcinoma (HCC). We present the results of this study in Chinese patients. Methods. In a multicenter, open-label, randomized, phase III study (NCT00471965), 371 patients (279 patients from the People's Republic of China) were randomized 1:1 to receive either FOLFOX4 or doxorubicin until disease progression, intolerable toxicity, death, or surgical resection. Results. Baseline characteristics of the Chinese patients enrolled in the study were similar for the 2 treatment groups and in comparison with the whole EACH cohort. Median OS at the prespecified time point of treatment was 5.7 months with FOLFOX4 and 4.3 months with doxorubicin (hazard ratio [HR]:

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of the FOLFOX4 Regimen Versus Doxorubicin in Chinese Patients With Advanced Hepatocellular Carcinoma: A Subgroup Analysis of the EACH Study

et al. 2014

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“…Most targeted molecular agents work by inhibiting kinases involved in tumor angiogenesis; angiogenesis is highly associated with local tumor progression as well as tumor invasion and metastasis [60]. Hypoxia, an important precipitating factor for angiogenesis, can be induced by incomplete tumor ablation.…”

Section: Rfa-combined Multimodal Therapiesmentioning

confidence: 99%

“…In addition to sorafenib and bevacizumab, there are a number of additional targeted molecular agents against HCC currently in various clinical trial phases, such as sunitinib and linifanib [60,79,80]. However, only few of these new drugs have been reported to be used in combination with RFA so far.…”

Section: Rfa-combined Multimodal Therapiesmentioning

confidence: 99%

Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status

2016

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Radiofrequency ablation (RFA) is widely accepted as a first-line interventional oncology approach for hepatocellular carcinoma (HCC) and has the advantages of high treatment efficacy and low complication risk. Local control rates equivalent to hepatic resection can be reached by RFA alone when treating small HCCs (<2 cm) in favorable locations. However, local tumor progression and recurrence rates with RFA monotherapy increase sharply when treating larger lesions (>3 cm). To address this clinical problem, recent efforts have focused on multimodel management of HCC by combining RFA with different techniques, including percutaneous ethanol injection, transarterial chemo-embolization, targeted molecular therapy, nanoparticle-mediated therapy, and immunotherapy. The combination strategy indeed leads to better outcomes in comparison to RFA alone. In this article, we review the current status of RFA-combined multimodal therapies in the management of HCC.

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“…Therefore, alternative agents with lower toxicities and higher efficacy are needed. To date, studies of other agents, including the mTOR inhibitor (everolimus), and other tyrosine kinase inhibitors (TKI), including sunitinib, linifanib, brivanib, and erlotinib, have failed to demonstrate improvements in OS (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

Ikeda

Okusaka

Mitsunaga

et al. 2016

Clinical Cancer Research

164

139

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Purpose: To determine the maximum tolerable dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of lenvatinib in patients with advanced hepatocellular carcinoma (HCC).Experimental Design: This multicenter, open-label, phase I, dose-escalation study included patients aged 20 to 80 years, refractory to standard therapy, and stratified by hepatic function measured using Child-Pugh (CP) scores: CP-A (score, 5-6) and CP-B (score, 7-8). Lenvatinib was administered continually once daily for 4-week cycles. MTD was defined as the maximum dose associated with 1 dose-limiting toxicity (DLT) occurring in cycle 1 among 6 patients.Results: In total, 20 patients (9 in CP-A and 11 in CP-B) were enrolled. The MTD was 12 and 8 mg once daily in CP-A and CP-B, respectively; DLTs included proteinuria, hepatic encephalopathy, and hyperbilirubinemia. The most common grade 3 toxicities included hypertension in CP-A and hyperbilirubinemia in CP-B. Lenvatinib plasma concentration at 24 hours after administration (C 24 h ) for 12 mg once daily was higher in patients with HCC than in patients with other solid tumors shown in a previous phase I study, but C 24 h for 25 mg once daily lenvatinib was comparable. After lenvatinib treatment, the number of circulating endothelial and c-Kit þ cells decreased and the levels of interleukin (IL)-6, IL10, granulocyte-colony stimulating factor, and vascular endothelial growth factor increased (P < 0.05). Partial responses were observed in 3 patients and tumor shrinkage occurred in 14 patients. Conclusions: Lenvatinib (12 mg once daily) demonstrated preliminary efficacy with manageable toxicity and is the recommended dose for phase II studies in patients with HCC and CP-A.

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New agents on the horizon in hepatocellular carcinoma

Cited by 19 publications

References 46 publications

Efficacy and Safety of the FOLFOX4 Regimen Versus Doxorubicin in Chinese Patients With Advanced Hepatocellular Carcinoma: A Subgroup Analysis of the EACH Study

Efficacy and Safety of the FOLFOX4 Regimen Versus Doxorubicin in Chinese Patients With Advanced Hepatocellular Carcinoma: A Subgroup Analysis of the EACH Study

Radiofrequency ablation-combined multimodel therapies for hepatocellular carcinoma: Current status

Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

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