机构：[1]Department of Neurosurgery and Neuro-oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.[2]Department of Radiation, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.[3]Department of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.深圳市第二人民医院深圳市康宁医院深圳医学信息中心[4]Department of Neuro-oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China.[5]Department of Clinical Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.[6]Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.[7]Department of Neurosurgery, Guangdong Sanjiu Brain Hospital, Guangzhou, China.[8]Department of Neurosurgery, Shantou Central Hospital, Shantou, China.[9]Department of Radiation Oncology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China.深圳市康宁医院深圳市人民医院深圳医学信息中心[10]The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China.[11]Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.广东省中医院[12]Guangdong Province Hospital of Chinese Medical, Guangzhou, China.[13]Department of Neurosurgery, Tumor Hospital of Harbin Medical University, Harbin, China.[14]Department of Radiotherapy, The Second Hospital of Hebei Medical University, Shijiazhuang, China.[15]Department of Medical Oncology, The First Affiliated Hospital, Jinan University, Guangzhou, China.[16]Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.[17]Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.[18]Neurosurgical Institute of Fudan University and Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.[19]Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China.[20]Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.[21]Department of Oncology, Guangdong Armed Police Corps Hospital, Guangzhou, China.[22]Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.[23]Department of Radiation Oncology, First People's Hospital of Fo Shan Affiliated with Sun Yat-Sen University, Foshan, China.[24]Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
High-grade gliomas (HGGs) constitute the most common and aggressive primary brain tumor, with 5-year survival rates of 30.9% for grade 3 gliomas and 6.6% for grade 4 gliomas. The add-on efficacy of interferon alfa is unclear for the treatment of HGG.To compare the therapeutic efficacy and toxic effects of the combination of temozolomide and interferon alfa and temozolomide alone in patients with newly diagnosed HGG.This multicenter, randomized, phase 3 clinical trial enrolled 199 patients with newly diagnosed HGG from May 1, 2012, to March 30, 2016, at 15 Chinese medical centers. Follow-up was completed July 31, 2021, and data were analyzed from September 13 to November 24, 2021. Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed HGG and had received no prior chemotherapy, radiotherapy, or immunotherapy for their HGG.All patients received standard radiotherapy concurrent with temozolomide. After a 4-week break, patients in the temozolomide with interferon alfa group received standard temozolomide combined with interferon alfa every 28 days. Patients in the temozolomide group received standard temozolomide.The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability.A total of 199 patients with HGG were enrolled, with a median follow-up time of 66.0 (95% CI, 59.1-72.9) months. Seventy-nine patients (39.7%) were women and 120 (60.3%) were men, with ages ranging from 18 to 75 years and a median age of 46.9 (95% CI, 45.3-48.7) years. The median OS of patients in the temozolomide plus interferon alfa group (26.7 [95% CI, 21.6-31.7] months) was significantly longer than that in the standard group (18.8 [95% CI, 16.9-20.7] months; hazard ratio [HR], 0.64 [95% CI, 0.47-0.88]; P = .005). Temozolomide plus interferon alfa also significantly improved median OS in patients with O6-methylguanine-DNA methyltransferase (MGMT) unmethylation (24.7 [95% CI, 20.5-28.8] months) compared with temozolomide (17.4 [95% CI, 14.1-20.7] months; HR, 0.57 [95% CI, 0.37-0.87]; P = .008). Seizure and influenzalike symptoms were more common in the temozolomide plus interferon alfa group, with 2 of 100 (2.0%) and 5 of 100 (5.0%) patients with grades 1 and 2 toxic effects, respectively (P = .02). Finally, results suggested that methylation level at the IFNAR1/2 promoter was a marker of sensitivity to temozolomide plus interferon alfa.Compared with the standard regimen, temozolomide plus interferon alfa treatment could prolong the survival time of patients with HGG, especially the MGMT promoter unmethylation variant, and the toxic effects remained tolerable.ClinicalTrials.gov Identifier: NCT01765088.
基金：
This work was supported by grant 81872059 from the National Natural Science Foundation of
China (Dr Zhongping Chen), grant 2019A1515010702 from the Natural Science Foundation of Guangdong (Dr Guo),
grant 202002030114 from the Science, Technology Program of Guangzhou (Dr Guo), and grant CSNO-2013-
MSD013 from the Chinese Society of Neuro-oncology (Dr Q. Yang).
第一作者机构：[1]Department of Neurosurgery and Neuro-oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
通讯作者：
通讯机构：[1]Department of Neurosurgery and Neuro-oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.[*1]Department of Neurosurgery and Neuro-oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, No. 651 Dongfeng East Rd, Guangzhou 510060, China
推荐引用方式(GB/T 7714)：
Guo Chengcheng,Yang Qunying,Xu Pengfei,et al.Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial[J].JAMA NETWORK OPEN.2023,6(1):doi:10.1001/jamanetworkopen.2022.53285.
APA：
Guo Chengcheng,Yang Qunying,Xu Pengfei,Deng Meiling,Jiang Taipeng...&Chen Zhongping.(2023).Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial.JAMA NETWORK OPEN,6,(1)
MLA：
Guo Chengcheng,et al."Adjuvant Temozolomide Chemotherapy With or Without Interferon Alfa Among Patients With Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial".JAMA NETWORK OPEN 6..1(2023)
医学