Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update

The "Guideline on the Use of New Anticancer Drugs for the Treatment of Hepatocellular Carcinoma" was prepared by the Study Group on New Liver Cancer Therapies established by the "Research Project on Emergency Measures to Overcome Hepatitis" under the auspices of the Health and Labour Sciences Research Grant. The Guideline brings together data collected by the Study Group on the use and incidence of adverse events in 264 patients with advanced hepatocellular carcinoma (HCC) treated using sorafenib and in 535 patients with advanced HCC treated using miriplatin at 16 participating institutions up until 22 December 2010, as well as referring to the published studies, academic presentations, and reports from the private sector. The aim of this Guideline is to facilitate understanding and current thinking regarding the proper usage of new anticancer drugs towards actual use in therapy. In terms of the format, the Guideline presents "clinical questions" on issues pertaining to medical care, makes "recommendations" on diagnosis and treatment in response to each of these clinical questions, and provides a rationale for these recommendations in the form of "scientific statements". © 2012 The Japan Society of Hepatology

カガク リョウホウカ 二 アル マッキ カンサイボウ ガン カンジャ ノ アエン ケツボウ

末期肝細胞癌患者では栄養状態の悪化が多く見られ,これは予後を左右する重要な因子である。化学療法目的で入院した 33名の IV 期肝細胞癌患者で,食事摂取状況と臨床検査データとの関連を調べた。血清中の直接ビリルビン,間接ビリルビン,LDH, AST, ALT, ALP, アルブミン,CRP, AFP さらに入院中の平均食事摂取率,食事摂取量,摂取エネルギー量,摂取食塩相当量,鉄摂取量,亜鉛摂取量,ビタミンK 摂取量および年齢を変数として重相関分析を行った。食事摂取率に影響を及ぼしているものは CRP と AFP であり,CRP に影響を及ぼしているものは亜鉛摂取量であった。亜鉛摂取量に影響を及ぼしているものは CRP と AFP であり,亜鉛摂取量はアルブミンにも影響を及ぼしていた。以上の結果から,亜鉛欠乏は本病状と深い関係があることを示しており,これらの患者においてこの問題を改善することが必要と考える。Malnutrition frequently occurs in end-stage hepatocellular carcinoma patients, and can influence survival in the patients. The objective of the present study was to investigate the relationships between clinical and dietary indices in the patients. The clinical data of 33 patients affected by hepatocellular carcinoma (stage IV) who had been hospitalized to receive chemotherapy were retrospectively analyzed. A multiple regression analysis was performed based on the blood data (albumin, total bilirubin, direct bilirubin, AST, ALT, LDH, ALP, -fetoprotein, and C-reactive protein) and the mean values of daily dietary indices (intake rate, dietary intake, energy intake, NaCl intake, iron intake, zinc intake, and vitamin K intake) during hospitalization. Both the intake rate and the zinc intake were significantly correlated with the C-reactive protein and -fetoprotein levels, while the albumin level was significantly correlated with the zinc intake and the ALT level. These results showed that zinc deficiency is correlated with a relatively poor prognosis. Thus, it is necessary to improve the problem in the affected patients

Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial

Background Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. Methods We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0–1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m 2 on days 1 and 8 and fluorouracil 330 mg/m 2 continuously on days 1–5 and 8–12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. Findings Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1–14·5] vs 11·5 months [8·2–14·8]; hazard ratio 1·009 [95% CI 0·743–1·371]; p=0·955). Grade 3–4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). Interpretation Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. Funding Japanese Ministry of Health, Labour and Welfare

A study on prevention of bleeding complications using lusutrombopag for safe RFA in patients with hepatocellular carcinoma with low platelet counts: prospective observational study

Abstract Background Platelet (PLT) transfusion was the most practical way to increase patients’ PLT counts before invasive hepatic procedures such as radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). A novel drug that raises the PLT count by acting on the thrombopoietin receptor has recently become available. Methods Lusutrombopag 3 mg was administered daily for 7 days to patients who underwent RFA for liver tumors with low PLT counts ( 50,000 PLT µL− 1 had higher PLT counts before lusutrombopag administration. The degree of splenomegaly did not affect the rate of PLT count elevation. There was no specific adverse effect by administrating lusutrombopag for patients with PLT counts of around 50,000 µL− 1 but > 50,000 µL− 1. Conclusions Lusutrombopag administration before RFA was effective and seemed to be relatively safe for hepatocellular carcinoma patients with low PLT counts. Trial registration This study was approved by Japanese Red Cross Medical Center Institutional Reseach Comittie (#862, 07/03/2016), and was registered in a publically accessible primary register (#UMIN000046629, registered date: 14/01/2022)