Recent advances in hepatocellular carcinoma therapy

// Peisi Kou 1,2,* , Yan Zhang 2,* , Wenbo Shao 4 , Hui Zhu 2 , Jingze Zhang 2 , Haiyong Wang 2 , Li Kong 2 and Jinming Yu 2,3,1 1 Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China 3 School of Medicine and Life Sciences, University of Jinan - Shandong Academy of Medical Sciences, Jinan, China 4 Department of Intervention, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China * These authors have contributed equally to this work Correspondence to: Jinming Yu, email: // Keywords : hepatocellular carcinoma, apatinib, targeted therapy Received : September 06, 2016 Accepted : January 04, 2017 Published : January 18, 2017 Abstract Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m 2 on day 1, calcium levofolinate 200 mg/m 2 on day 1 and 2, 5-fluorouracil 400 mg/m 2 intravenously and 5-fluorouracil 600 mg/m 2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients.

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Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.

Metronomic S-1 chemotherapy and vandetanib : an efficacious and nontoxic treatment for hepatocellular carcinoma

Potential role of metronomic chemotherapy in the treatment of esophageal and gastroesophageal cancer

Transarterial chemoembolization (TACE) is widely applied for the treatment of hepatocellular carcinoma. Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session. However, repeated TACE procedures can impair liver function and increase treatment-related adverse events, all of which prompted the introduction of the concept of “TACE failure/refractoriness”. Mainly based on evidence from two retrospective studies conducted in Japan, sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness. Several studies have investigated the outcomes of other subsequent treatments, including locoregional, other molecular targeted, anti-programmed death-1/anti-programed death ligand-1 therapies, and combination therapies after TACE failure/refractoriness. In this review, we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence

Purpose To assess the efficacy and safety of metronomic S-1 chemotherapy combination with transcatheter arterial chemoembolization (TACE) for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) refractory to TACE. Methods Twenty six patients met the eligibility criteria and were enrolled. TACE was performed on day 1, and metronomic S-1 chemotherapy on days 2-15. Tumor assessment was performed one month later. The primary endpoints were time to progression (TTP) and adverse events (AE). Results Twenty six patients in total received 176 TACE interventions. There were 101 TACE interventions in 15 patients of metronomic S-1 chemotherapy plus TACE (TS) and 75 in 11 patients of TACE monotherapy (TM). Fifteen TS patients received a total of 55 cycles of treatment with S-1, with a median of 4 cycles (range 2-6). The total dose of S-1 was 6165 mg per day in 15 patients (average 120 mg, range 100-125). Median TTP and overall survival (OS) of TS group were 6 months (95% CI, 4.7-7.3) and 17 months (95% CI, 15.6-18.4), respectively, while for the TM group were 4 months (95% CI, 2.4-5.6) and 15 months (95% CI, 9.2-20.8), respectively. Though there were higher tumor response rate (RR) and disease control rates (DCRs) in patients with TS, no significant differences were detected. Both treatment approaches were tolerable with low grade AE. Conclusions In the present study, metronomic S-1 chemotherapy plus TACE in the present study was tolerable and associated with a better but not statistically significant TTP, RR and OS. It showed that metronomic S-1 chemotherapy plus TACE may be a promising treatment of BCLC Stage B HCC refractory to TACE.

Metronomic S-1 chemotherapy plus transcatheter arterial chemoembolization (TACE): a promising treatment of hepatocellular carcinoma refractory to TACE.

Purpose To assess the efficacy and safety of S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma (HCC). Methods PubMed, the Cochrane Library, EMBASE, and ClinicalTrials.gov were searched using the terms "Hepatocellular Carcinoma" or "HCC" or "Hepatoma" or "Liver cancer" and "S-1" and "Sorafenib" or "Nexavar". Outcomes of main interest included overall survival (OS) and toxicities. Results We identified 2 studies of S"1 plus sorafenib from 77 references that included a total of 65 patients. The percentage of male patients ranged from 70.0 to 89.5%. Median age was 59.2 years and ranged from 48.0 to 65.5 years. The percentage of hepatitis B virus ranged from 23.1 to 90.0%. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m2/day and 800 mg/day, respectively and treatment was administered orally on days 1-14 and days 1-21, respectively. Median OS were 10.4 and 10.5 months, respectively. The incidence of all-grade toxicities of more than 30% were hand"foot syndrome (HFS) and rash. The incidence of grade 3/4 toxicities more than 5% were thrombocytopenia, elevated AST/ALT and hyperbilirubinemia. Conclusion This systematic review suggests that S-1 plus sorafenib showed modest clinical efficacy and tolerable toxicity profile in patients with advanced HCC. The recommended dose of S-1 and sorafenib was 80 or 64 mg/m2/day and 800 mg/day, respectively.

S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma.

Abstract The results tested by the impact-echo method of the small-size short cylinder/circular tube structure were fundamentally different from that of the large-size long one. This phenomenon cannot be described by the existing calculation formulas. To modify the classical calculation formula, finite element models of various sizes of small-size short cylinder/circular tube structures, including 80 cylinders and 125 circular tubes, were established. Modal analysis frequency was compared with numerical simulation of impact-echo frequency under partial working conditions. In addition, the impact-echo frequency of whole working conditions was counted for later analysis. The impact-echo frequency correction formulas of the small-size short cylinder/circular tube considering the model length and the cross-sectional size of the cylinder/circular tube were proposed. Moreover, their reliabilities were verified through tests. The results showed that the impact-echo frequency of the small-size short cylinder structure increased linearly with the increase in diameter, decreased with the increase in length, whereas the relationship among frequency, outer diameter, and wall thickness of the circular tube component was complicated. Moreover, the modal of the whole member was excited rather than the free modal of the cross section of the large-size cylinder/circular tube when the small-size short one was impacted.

Abulajiang Abulikemu

Papers

Metronomic S-1 chemotherapy plus transcatheter arterial chemoembolization (TACE): a promising treatment of hepatocellular carcinoma refractory to TACE.

S-1 plus sorafenib for the treatment of advanced hepatocellular carcinoma.

Shape coefficient of impact-echo for small-size short cylinder/circular tube structures