Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenva...Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.展开更多
Primary liver cancer is a significant health problem worldwide.Hepatocellular carcinoma(HCC)is the main pathological type of primary liver cancer,accounting for 75%-85%of cases.In recent years,radiotherapy has become ...Primary liver cancer is a significant health problem worldwide.Hepatocellular carcinoma(HCC)is the main pathological type of primary liver cancer,accounting for 75%-85%of cases.In recent years,radiotherapy has become an emerging treatment for HCC and is effective for various stages of HCC.However,radiosensitivity of liver cancer cells has a significant effect on the efficacy of radiotherapy and is regulated by various factors.How to increase radiosensitivity and improve the therapeutic effects of radiotherapy require further exploration.This review summarizes the recent research progress on the mechanisms affecting sensitivity to radiotherapy,including epigenetics,transportation and metabolism,regulated cell death pathways,the microenvironment,and redox status,as well as the effect of nanoparticles on the radiosensitivity of liver cancer.It is expected to provide more effective strategies and methods for clinical treatment of liver cancer by radiotherapy.展开更多
基金financially supported by the Science and Technology Plan Project of Guangzhou (No. 202102010171)National Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University (No. 2020GZRPYMS11)+2 种基金Natural Science Foundation of Guangdong Province (No. 2018A030313641)Natural Science Foundation of Guangdong Province (No. 2016A030313848)Science and Technology Plan Project of Guangzhou (No. 201704020175)。
文摘Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.
基金supported by the Science and Technology Plan Project of Guangzhou(No.202102010171)National Natural Science Foundation Cultivation Project of The Third Affiliated Hospital of Sun Yat-sen University(No.2020GZRPYMS11)+1 种基金Natural Science Foundation of Guangdong Province(No.2018A030313641)CSCO-Roche Joint Cancer Research Fund(No.Y-Roche2019/20041)。
文摘Primary liver cancer is a significant health problem worldwide.Hepatocellular carcinoma(HCC)is the main pathological type of primary liver cancer,accounting for 75%-85%of cases.In recent years,radiotherapy has become an emerging treatment for HCC and is effective for various stages of HCC.However,radiosensitivity of liver cancer cells has a significant effect on the efficacy of radiotherapy and is regulated by various factors.How to increase radiosensitivity and improve the therapeutic effects of radiotherapy require further exploration.This review summarizes the recent research progress on the mechanisms affecting sensitivity to radiotherapy,including epigenetics,transportation and metabolism,regulated cell death pathways,the microenvironment,and redox status,as well as the effect of nanoparticles on the radiosensitivity of liver cancer.It is expected to provide more effective strategies and methods for clinical treatment of liver cancer by radiotherapy.
