Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
文献类型：期刊论文
| 作者 | Li, Huiping2; Liu, Rongrui3; Shao, Bin2; Ran, Ran2; Song, Guohong2; Wang, Ke4; Shi, Yehui4; Liu, Jihong5; Hu, Wenjing6; Chen, Fu2 |
| 刊名 | CHINESE JOURNAL OF CANCER RESEARCH
 |
| 出版日期 | 2020-06-01 |
| 卷号 | 32期号:3页码:370-+ |
| 关键词 | Phase I PARP inhibitor (fluzoparib) solid tumor pharmacokinetics safety antitumor activity |
| ISSN号 | 1000-9604 |
| DOI | 10.21147/j.issn.1000-9604.2020.03.08 |
| 通讯作者 | Li, Huiping(huipingli2012@hotmail.com) ; Xu, Jianming(jmxu2003@yahoo.com) |
| 英文摘要 | Objective: Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer. Methods: This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patients with ovarian cancer (OC). Fluzoparib was administered orally once or twice daily (bid) at 11 dose levels from 10 to 400 mg/d. Endpoints included dose-finding, safety, pharmacokinetics, and antitumor activity. Results: Seventy-nine patients were enrolled from March, 2015 to January, 2018 [OC (47, 59.5%); breast cancer (BC) (16, 20.3%); colorectal cancer (8, 10.1%), other tumors (8, 10.1%)]; 48 patients were treated in the D-Esc arm and 31 in the D-Ex arm. The maximum tolerated dose (MTD) was 150 mg bid, with a half-life of 9.14 h. Grade 3/4 adverse events included anemia (7.6%) and neutropenia (5.1%). The objective response rate (ORR) was 30% (3/10) in patients with platinum-sensitive OC and 7.7% (1/13) in patients with BC. Among patients treated with fluzoparib >= 120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8-9.3] months in OC, 9.3 (95% CI, 7.2-9.3) months in platinum-sensitive OC, and 3.5 (range, 2.0-28.0) months in BC. In patients with germline BC susceptibility gene mutation (gBRCA(Mut)) (11/43 OC; 2/16 BC), mPFS was 8.9 months for OC (range, 1.0-23.2; 95% CI, 1.0-16.8) and 14 and 28 months for BC (those two patients both also had somatic BRCA(Mut)). Conclusions: The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in BRCAMut and platinum-sensitive OC. |
| WOS关键词 | METASTATIC BREAST-CANCER ; GRADE OVARIAN-CARCINOMA ; GERMLINE BRCA MUTATION ; MAINTENANCE THERAPY ; MULTICENTER TRIAL ; DOUBLE-BLIND ; OLAPARIB ; RUCAPARIB ; EFFICACY ; CARRIERS |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000546360200008 |
| 出版者 | CHINESE JOURNAL CANCER RESEARCH CO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291928]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Huiping; Xu, Jianming |
| 作者单位 | 1.Jiangsu Hengrui Med Co Ltd, Dept Clin Med Oncol, Shanghai 201203, Peoples R China 2.Peking Univ Canc Hosp & Inst, Dept Breast Oncol, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China 3.Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Gastrointestinal Oncol, Beijing 100071, Peoples R China 4.Tianjin Med Univ Canc Inst & Hosp, Dept Gynecol Oncol, Tianjin 300060, Peoples R China 5.Sun Yat Sen Univ, Canc Ctr, Dept Gynecol Oncol, Guangzhou 510060, Peoples R China 6.Nanjing Univ, Med Sch, Affiliated Drum Tower Hosp, Drum Tower Hosp,Comprehens Canc Ctr, Nanjing 210008, Peoples R China 7.Univ Calif San Francisco, Dept Med, Comprehens Canc Ctr, San Francisco, CA 94127 USA 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Huiping,Liu, Rongrui,Shao, Bin,et al. Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors[J]. CHINESE JOURNAL OF CANCER RESEARCH,2020,32(3):370-+. |
| APA | Li, Huiping.,Liu, Rongrui.,Shao, Bin.,Ran, Ran.,Song, Guohong.,...&Xu, Jianming.(2020).Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors.CHINESE JOURNAL OF CANCER RESEARCH,32(3),370-+. |
| MLA | Li, Huiping,et al."Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors".CHINESE JOURNAL OF CANCER RESEARCH 32.3(2020):370-+. |
入库方式： OAI收割
来源：上海药物研究所
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