Adjuvant Temozolomide Chemotherapy with or Without Interferon Alfa among Patients with Newly Diagnosed High-grade Gliomas: A Randomized Clinical Trial

Guo，Chengcheng1; Yang，Qunying1; Xu，Pengfei1; Deng，Meiling2; Jiang，Taipeng3; Cai，Linbo4; Li，Jibin5; Sai，Ke1; Xi，Shaoyan6; Ouyang，Hui7; Liu，Mingfa8; Li，Xianming9,10; Li，Zihuang9,10; Ni，Xiangrong1; Cao，Xi1; Li，Cong11,12; Wu，Shaoxiong2; Du，Xiaojing2; Su，Jun13; Xue，Xiaoying14; Wang，Yiming15; Li，Gang16; Qin，Zhiyong17,18,19; Yang，Hui20; Zhou，Tao21; Liu，Jinquan22; Hu，Xuefeng23; Wang，Jian1; Jiang，Xiaobing1; Lin，Fuhua1; Zhang，Xiangheng1; Ke，Chao1; Lv，Xiaofei24; Lv，Yanchun24; Hu，Wanming6; Zeng，Jing6; Chen，Zhenghe1; Zhong，Sheng1; Wang，Hairong1; Chen，Yinsheng1; Zhang，Ji1; Li，Depei1; Mou，Yonggao1; Chen，Zhongping1

2023-01-27

10.1001/jamanetworkopen.2022.53285

JAMA Network Open   影响因子和分区

2574-3805

2574-3805

Importance: 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. Objectives: 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. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: The primary end point was 2-year overall survival (OS). Secondary end points were 2-year progression-free survival (PFS) and treatment tolerability. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01765088.

SCI

英语

其他

National Natural Science Foundation of China[81872059] ; Natural Science Foundation of Guangdong[2019A1515010702] ; Science, Technology Program of Guangzhou[202002030114] ; Chinese Society of Neuro-oncology[CSNO-2013-MSD013]

General & Internal Medicine

Medicine, General & Internal

WOS:001059389500004

AMER MEDICAL ASSOC

2-s2.0-85147092447

Scopus

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
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
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
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,Fudan University,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,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

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).

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).

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).