Rongcheng Luo

Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial

BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. METHODS Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752. FINDINGS 271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6.5 months (95% CI 5.56-7.56) in patients treated with sorafenib, compared with 4.2 months (3.75-5.46) in those who received placebo (hazard ratio [HR] 0.68 [95% CI 0.50-0.93]; p=0.014). Median TTP was 2.8 months (2.63-3.58) in the sorafenib group compared with 1.4 months (1.35-1.55) in the placebo group (HR 0.57 [0.42-0.79]; p=0.0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10.7%]), diarrhoea (nine patients [6.0%]), and fatigue (five patients [3.4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11.4%]) and diarrhoea (11 patients [7.4%]); these adverse events rarely led to discontinuation. INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma.

Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial

BACKGROUND Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is non-inferior to gefitinib in patients with non-small-cell lung cancer. METHODS In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18-75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. FINDINGS 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67-1·05; median progression-free survival 4·6 months [95% CI 3·5-6·3] vs 3·4 months [2·3-3·8]; p=0·13). The most common adverse events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of 199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 [61%] vs 140 [70%]; p=0·046), especially drug-related diarrhoea (37 [19%] vs 55 [28%]; p=0·033). INTERPRETATION Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer.

Platinum-based chemotherapy plus cetuximab first-line for Asian patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Results of an open-label, single-arm, multicenter trial.

The purpose of this study was to assess the efficacy, safety, and pharmacokinetics of cisplatin‐based chemotherapy plus cetuximab as first‐line treatment in Chinese and Korean patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).

China experts consensus on the diagnosis and treatment of advanced stage primary lung cancer (2016 version)

Yuankai SHI, Yan SUN, Jinming YU, Cuimin DING, Ziping WANG, Changli WANG, Dong WANG, Cunde WANG, Zheng WANG, Mengzhao WANG, Xiuyi ZHI, You LU, Jifeng FENG, Yunpeng LIU, Xiaoqing LIU, Wei LIU, Gang WU, Xiaomei LI, Kai LI, Enxiao LI, Wei LI, Gongyan CHEN, Zhengtang CHEN, Ping YU, Ning WU, Milu WU, Wenhua XIAO, Li ZHANG, Yiping ZHANG, Shucai ZHANG, Shujun YANG, Xia SONG, Dongmei LIN, Rongcheng LUO, Li SHAN, Caicun ZHOU, Zongmei ZHOU, Qiong ZHAO, Chengping HU, Yi HU, Qisen GUO, Jianhua CHANG, Cheng HUANG, Xuan ZENG, Baohui HAN, Xiaohong HAN, Bo JIA, Ying HAN and Yu HUANG 1Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 4Beijing Cancer Hospital, 9Peking Union Medical College Hospital, 10Beijing Xuanwu Hospital, Capital Medical University, 14The 307th Hospital of Chinese People’s Liberation Army, 16Chinese People’s Liberation Army General Hospital, 22Department of Imaging Diagnostic, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 24The First Affiliated Hospital of Chinese People’s Liberation ArmyGeneral Hospital, 26Beijing Chest Hospital, Capital Medical University, Beijing, 36Shanghai Chest Hospital, Shanghai Jiaotong University, 31Shanghai PulmonaryHospital, Tongji University, 34Cancer Hospital, FudanUniversitay, Shanghai, 2Shandong Province Cancer Hospital, Ji’nan, 3The Fourth Hospital of HebeiMedical University, Shijiazhuang, 5Tianjin Medical University Cancer Institute & Hospital, Tianjin, 6Daping Hospital, The Third Military Medical University, Chongqing, 20Xinqiao Hospital of The Third Military Medical University, Chongqing, 7Yunnan Province Cancer Hospital, Kunming, 11West China Hospital of Sichuan University, Chengdu, 21Sichuan Cancer Hospital, Chengdu, 12Jiangsu Cancer Hospital, Nanjing, 13The First Hospital of China Medical University, Shenyang, 15Huazhong University of Science and Technology Union Hospital, Wuhan, 17The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an, 18The First Hospital of Jilin University, Changchun, 19HarbinMedical University Cancer Hospital, Harbin, 23Qinghai University Affiliated Hospital, Xining, 25Zhejiang Cancer Hospital, Hangzhou, 32The First Affiliated Hospital, Zhejiang University, Hangzhou, 27Henan Province Cancer Hospital, Zhengzhou, 28Shanxi Province Cancer Hospital, Taiyuan, 29Nanfang Hospital, Nanfang Medical University, Guangzhou, 30Cancer Hospital of Xinjiang Medical University, Urumqi, 33Xiangya Hospital, Central South University, Changsha, and 35Fujian Cancer Hospital, Fuzhou, China

The efficacy and safety of icotinib in patients with advanced non-small cell lung cancer previously treated with chemotherapy: A single-arm, multi-center, prospective study

Background Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. Methods Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety. Results From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127). Conclusions In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy. Trial Registration ClinicalTrials.gov NCT02486354

China experts consensus on icotinib for non-small cell lung cancer treatment (2015 version)

According to Chinese Cancer Registry Annual Report in 2011, the incidence rate of lung cancer was 48.32/100,000 and the mortality rate was 39.27/100,000 in China in 2011, being the highest among all cancers (1). Most patients with nonsmall cell lung cancer (NSCLC) which accounts for 85% of all lung cancers have entered the advanced stage at the first visit to hospital and thus missed the opportunity for surgery. As the main treatment for advanced NSCLC, chemotherapy has reached a plateau in its efficacy and has been restricted in clinical application due to adverse reactions. In recent years, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), thanks to their definite efficacy, mild adverse reaction and convenience for oral use, have broken the bottleneck of traditional chemotherapeutic drugs and become an essential treatment for advanced NSCLC.

China experts consensus on icotinib for non-small cell lung cancer treatment (2015 version).

According to Chinese Cancer Registry Annual Report in 2011, the incidence rate of lung cancer was 48.32/100,000 and the mortality rate was 39.27/100,000 in China in 2011, being the highest among all cancers (1). Most patients with non-small cell lung cancer (NSCLC) which accounts for 85% of all lung cancers have entered the advanced stage at the first visit to hospital and thus missed the opportunity for surgery. As the main treatment for advanced NSCLC, chemotherapy has reached a plateau in its efficacy and has been restricted in clinical application due to adverse reactions. In recent years, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), thanks to their definite efficacy, mild adverse reaction and convenience for oral use, have broken the bottleneck of traditional chemotherapeutic drugs and become an essential treatment for advanced NSCLC.

Renoprotective Effect of a Chinese Herbal Formula, Qidan Dihuang Decoction, on Streptozotocin-Induced Diabetes in Rat

Qidan Dihuang decoction (QDD) is the latest development of Chinese medicine compound and mainly provides renal protection. The study presented was designed to evaluate the renoprotective effects of QDD on streptozotocin-induced diabetes and to explore the possible mechanisms of this action. We established a diabetes rat model. The condition of the rats was observed. The biochemistry indexes for diabetic rats were examined. Renal tissues were stained with HE, PAS, and Masson and we performed immunohistochemical staining for α-SMA and TGF-β. The proteins expressions of α-SMA, TGF-β, renin, and AT1 were detected by western blot. After treatment for 8 weeks, serum creatinine and 24 h proteinuria were significantly reduced in the rats which received losartan and Qidan Dihuang decoction while blood glucose, urine volume, blood urea nitrogen, and KW/BW did not improve. The pathology of renal tissue of rats treated with losartan and Qidan Dihuang decoction was inhibited. In addition, western blot showed that the expression of α-SMA, TGF-β, renin, and AT1 proteins was significantly decreased after receiving Qidan Dihuang decoction and losartan. Taken together, the results indicate that Qidan Dihuang decoction can improve the renal function and inhibit renal fibrosis of DN rat via modulating RAS system.