Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia–Pacific trial

Cheng, Ann‐Lii; Guan, Zhi‐Zhong; Chen, Zhendong; Tsao, Chao Jung; Qin, Shukui; Kim, Jun Suk; Yang, Tsung‐Ming; Tak, Won Young; Pan, Hongming; Yu, Shiying; Xu, Jianming; Fang, Fang; Zou, J.; Lentini, Giuseppe; Voliotis, D.; Kang, Yoon Koo

doi:10.1016/j.ejca.2011.12.006

Cited by 237 publications

(208 citation statements)

References 28 publications

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“…In the SHARP study, the median overall survival (OS) times were 10.7 months in the sorafenib group and 7.9 months in the placebo group (P<0.001); and the median times to radiological progression were 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001) (9). The phase III Sorafenib Asia-Pacific trial, restricted to an eastern population, also showed that sorafenib could significantly prolong the median OS time from 4.2 to 6.5 months compared with placebo group (10). However, the objective response rates (ORRs) in these two trials were 2 and 3.3%, suggesting that the efficacy of sorafenib remained limited.…”

Section: Introductionmentioning

confidence: 89%

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

Yuan

Liang

et al. 2017

Molecular and Clinical Oncology

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Abstract. Sorafenib is currently the only efficient molecular targeted therapy for hepatocellular carcinoma (HCC), although its effect is relatively moderate and variable between individuals. The present study aimed to evaluate the significance of peripheral blood neutrophils in the prognosis of HCC patients treated with sorafenib. A total of 464 patients with HCC were treated with sorafenib at Zhongshan Hospital (Shanghai, China) between January 1st, 2008 and December 31st, 2012, among which 120 patients were enrolled in the study. The optimal cutoff point for low vs. high neutrophil count (3.65x10 9 ) was obtained from a receiver operating characteristic curve. Overall survival (OS) was compared between the patients with low and high peripheral neutrophil counts. Univariate and multivariate analyses were used to explore the prognostic factors associated with OS in the patients treated with sorafenib. A nomogram model was also performed to predict the OS times of these patients. The median OS time was 9.0 months (95% confidence interval, 5.9-12.1 months) in the whole group of patients, with 1-, 2-and 3-year OS rates of 36, 24 and 16%, respectively. Using a cutoff level of 3.65x10 9 neutrophils/l, the median OS time was longer in the group of patients with a low peripheral neutrophil count than in those with a high peripheral neutrophil count (11.5 vs. 5.0 months, respectively; P<0.001). The multivariate analysis showed that peripheral neutrophil count, α-fetoprotein level and tumor size were independent prognostic factors for OS. In addition, using the nomogram model for the prediction of OS, the Harrell's c-index was 0.79. Therefore, it was concluded that a lower peripheral blood neutrophil count was associated with a better prognosis following treatment with sorafenib therapy.

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Section: Introductionmentioning

confidence: 89%

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

Yuan

Liang

et al. 2017

Molecular and Clinical Oncology

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“…For patients with vascular invasion and/or extrahepatic spread, i.e., whose tumors were classified as advanced stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system, the multi-kinase inhibitor sorafenib is recommended [4] . In recent randomized controlled trials, sorafenib significantly increased patient survival [5,6] . However, contrary to our expectations, the survival and therapeutic advantages of sorafenib are modest, and the current cost of the drug precludes sorafenib from becoming a more generalized treatment tool for advanced HCC [7] .…”

Section: Introductionmentioning

confidence: 99%

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

Song

Bae²,

Song³

et al. 2013

WJG

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AIM:To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS:Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS:Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.© 2013 Baishideng. All rights reserved. Key words: Hepatocellular carcinoma; Hepatic arterial infusion chemotherapy; Portal vein tumor thrombosisCore tip: The aim of this study was to investigate the prognostic factors of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma patients with portal vein tumor thrombosis. The primary findings of this study were as follows: (1) The median survival and time to progression were 7 and 2 mo, respectively; (2) A tumor volume of < 400 cm 3 and protein induced by vitamin K absence or antagonist-Ⅱ were independent pre-treatment prognostic factors; (3) Disease control and ≥ 50% tumor marker reduction were significant prognostic factors after the second cycle of hepatic arterial infusion chemotherapy (HAIC); and (4) Objective tumor response, disease control and portal vein tumor thrombosis response were independent post-treatment prognostic factors at the end of the HAIC. ORIGINAL ARTICLE

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“…Although several studies have investigated the prognostic factors in sorafenib treatment, no consensus factors have yet been identified (6)(7)(8)(9)(10)(11)(12). Pretreatment liver function parameters, such as Child-Pugh classification, serum bilirubin, serum albumin (ALB) and serum aminotransferase have been reported as prognostic factors in sorafenib treatment (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Pretreatment liver function parameters, such as Child-Pugh classification, serum bilirubin, serum albumin (ALB) and serum aminotransferase have been reported as prognostic factors in sorafenib treatment (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Impact of pretreatment serum cholinesterase level in unresectable advanced hepatocellular carcinoma patients treated with sorafenib

Takeda

Nishikawa

Iguchi

et al. 2012

Molecular and Clinical Oncology

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Abstract. The value of serum cholinesterase (ChE) level as a predictive marker in sorafenib therapy for advanced hepatocellular carcinoma (HCC) has not yet been investigated. The present retrospective study therefore analyzed the impact of the serum ChE level in 93 patients with advanced HCC treated with sorafenib. Patients were categorized into two groups: group A with pretreatment serum ChE ≥140 IU/l (n=46) and group B with pretreatment serum ChE <140 IU/l (n=47). The correlation between clinicopathological findings, including serum ChE level, and overall survival (OS) and liver damage during sorafenib therapy was investigated. The median OS of the patients was 275 days, while OS was markedly higher in group A compared to group B (P=0.002). In 70 Child-Pugh A patients, serum ChE level was a significant prognostic predictor in multivariate analysis [P=0.019, hazard ratio (HR) =2.612; 95% confidence interval (CI), 1.174-5.810]. During sorafenib treatment, 22 patients developed liver dysfunction of grade 3 or higher. Only two group A patients (4.3%) developed liver dysfunction, compared to 20 group B patients (42.6%) (P<0.001). Multivariate analysis demonstrated that the pretreatment serum ChE level was the strongest predictor of liver damage (P= 0.002, HR= 0.061, 95% CI: 0.010-0.373), indicating serum ChE <140 IU/l to be the only independent predictor associated with severe liver function damage during sorafenib treatment in 70 patients with grade A Child-Pugh (P= 0.016; HR= 0.122; 95% CI, 0.022-0.676). In conclusion, lower serum ChE level is a significant predictor of poor prognosis and severe liver damage in HCC patients treated with sorafenib. Advanced HCC patients with lower serum ChE levels, including those with a Child-Pugh A pretreatment liver function score, should be given sorafenib therapy with caution.

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Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia–Pacific trial

Cited by 237 publications

References 28 publications

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

Peripheral blood neutrophil count as a prognostic factor for patients with hepatocellular carcinoma treated with sorafenib

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

Impact of pretreatment serum cholinesterase level in unresectable advanced hepatocellular carcinoma patients treated with sorafenib

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