Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC).

Cheng, Ann‐Lii; Kang, Yubin; Deng, Lin; Park, J.; Kudo, M.; Qin, S.; Omata, Masao; Lowenthal, Susan W. Pitman; Lanzalone, Silvana; Yang, Lin; Lechuga, Mariajosé; Raymond, Éric

doi:10.1200/jco.2011.29.15_suppl.4000

Cited by 96 publications

(72 citation statements)

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“…A recent study has shown that HBV-positive HCC cells exhibit lower expression of microRNA193b targeting urokinase plasminogen activator and higher myeloid cell leukemia-1 protein levels, and increasing the expression of microRNA-193b increased the HCC cells response to sorafenib treatment [37]. In addition, treatment with sorafenib is associated with high incidence of toxicity events (e.g., diarrhea, hand-foot skin reaction, bleeding) and [38,39]. A number of monoclonal antibodies that bind the vascular endothelial growth factor and inhibit angiogenesis are currently under evaluation in phase II and III clinical trials [40][41][42][43].…”

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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“…With regard to HCC, the only systemic agent that has been shown to improve survival is sorafenib, an oral multikinase inhibitor (5,6). Beyond sorafenib, several studies are evaluating novel combinations (9), and although benefits have been observed with sorafenib, other single agents (e.g., sunitinib) have not shown efficacy in HCC (10).…”

Section: Introductionmentioning

confidence: 99%

Phase II, Open-Label Study of Brivanib as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma

Finn

Kang

Mulcahy

et al. 2012

Clinical Cancer Research

164

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Purpose: Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has recently been shown to have activity as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This phase II open-label study assessed brivanib as second-line therapy in patients with advanced HCC who had failed prior antiangiogenic treatment.Experimental Design: Brivanib was administered orally at a dose of 800 mg once daily. The primary objectives were tumor response rate, time to response, duration of response, progression-free survival, overall survival (OS), disease control rate, time to progression (TTP), and safety and tolerability.Results: Forty-six patients were treated. Best responses to treatment with brivanib (N ¼ 46 patients) using modified World Health Organization criteria were partial responses for two patients (4.3%), stable disease for 19 patients (41.3%), and progressive disease for 19 patients (41.3%). The tumor response rate was 4.3%; the disease control rate was 45.7%. Median OS was 9.79 months. Median TTP as assessed by study investigators following second-line treatment with brivanib was 2.7 months. The most common adverse events were fatigue, decreased appetite, nausea, diarrhea, and hypertension.Conclusion: Brivanib had a manageable safety profile and is one of the first agents to show promising antitumor activity in advanced HCC patients treated with prior sorafenib.

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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

154

134

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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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Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC).

Cited by 96 publications

References 0 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

Phase II, Open-Label Study of Brivanib as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma

Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

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