A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer.
A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer.
复制标题
DOI：
10.1016/j.clbc.2020.09.015
复制
发表时间：
2021-06
影响因子：
3.1
通讯作者：
Chang JC
中科院分区：
文献类型：
--
作者：
Anand K;Niravath P;Patel T;Ensor J;Rodriguez A;Boone T;Wong ST;Chang JC
化疗可以消灭除癌症干细胞以外的大部分癌细胞。氯喹是一种潜在的靶向癌症干细胞的药物。在这项针对蒽环类化疗难治性乳腺癌患者的II期试验中，我们将氯喹与紫杉烷或紫杉烷样化疗联合使用。联合治疗的总有效率为45%，高于单独化疗的预期总有效率30%。化疗消除了大部分癌细胞，除了那些具有自我更新和肿瘤形成潜力的癌细胞，即癌症干细胞（CSCs）。通过生物信息学研究，发现氯喹是一种潜在的靶向csc的药物。我们设计了一项II期试验，以测试氯喹联合紫杉烷或紫杉烷样化疗药物对蒽环类化疗难治性晚期或转移性乳腺癌患者的疗效和安全性。≥18岁且既往接受过蒽环类化疗的女性患者被纳入本研究。氯喹250 mg每日口服，每3周与多西紫杉醇或紫杉醇或nab-紫杉醇或伊沙匹龙联合服用。允许的最大3周周期数为6。主要疗效终点为客观有效率（ORR）。次要疗效终点包括无进展生存期（PFS）和安全性分析。38名患者参加了这项研究，其中31名患者进行了反应评估。中位年龄为54.1岁（范围31.7-78.1岁）。ORR为45.16%(95%可信区间[CI]， 29.2% ~ 62.2%)，高于预期的30% ORR （P = .03）。患者的中位随访时间为25.4个月，中位PFS为12.4个月（95% CI, 4.9-24.6个月），中位OS为25.4个月（95% CI, 13.7-83.5个月）。联合用药耐受性良好，只有13.15%的患者出现≥3级不良事件。氯喹联合紫杉烷或紫杉烷样化疗对既往有蒽环类化疗的局部晚期或转移性乳腺癌患者有效。
Chemotherapy eliminates most cancer cells except cancer stem cells. Chloroquine is a potential agent to target cancer stem cells. In this phase II trial for patients with breast cancer who were refractory to anthracycline-based chemotherapy, we combined chloroquine with taxane or taxane-like chemotherapy. The overall response rate of the combination was 45%, higher than the expected overall response rate of 30% with chemotherapy alone. Chemotherapy eliminates most of the cancer cells except those with potential for self-renewal and tumor initiation, called cancer stem cells (CSCs). Chloroquine, through bioinformatics, was found to be a potential agent to target CSCs. We designed a phase II trial to test the efficacy and safety of chloroquine in combination with taxane or taxane-like chemotherapy agents in patients with advanced or metastatic breast cancer who are refractory to anthracycline-based chemotherapy. Female patients ≥ 18 years of age who had received prior anthracycline chemotherapy were enrolled in this study. Chloroquine 250 mg was given daily orally with either docetaxel or paclitaxel or nab-paclitaxel or ixabepilone every 3 weeks. The maximum number of 3-week cycles allowed was 6. The primary efficacy endpoint was the objective response rate (ORR). The secondary efficacy endpoints included progression-free survival (PFS) and safety analysis. Thirty-eight patients were enrolled in the study, and 31 patients were evaluated for response. The median age was 54.1 years (range, 31.7–78.1 years). The ORR was 45.16% (95% confidence interval [CI], 29.2%–62.2%), which was higher than the expected ORR of 30% (P = .03). Patients were followed for a median of 25.4 months and experienced a median PFS of 12.4 months (95% CI, 4.9–24.6 months) and a median OS of 25.4 months (95% CI, 13.7–83.5 months). The combination was well-tolerated, with only 13.15% of patients experiencing grade ≥ 3 adverse events. A combination of chloroquine with taxane or taxane-like chemotherapy was efficacious in patients with locally advanced or metastatic breast cancer with prior anthracycline-based chemotherapy.
登录
查看更多内容
影响因子：
5.2
作者：
Choi, Dong Soon;Blanco, Elvin;Kim, Yoo-Shin;Rodriguez, Angel A.;Zhao, Hong;Huang, Tim Hui-Ming;Chen, Chun-Liang;Jin, Guangxu;Landis, Melissa D.;Burey, Lacey A.;Qian, Wei;Granados, Sergio M.;Dave, Bhuvanesh;Wong, Helen H.;Ferrari, Mauro;Wong, Stephen T. C.;Chang, Jenny C.
通讯作者：
Chang, Jenny C.
DOI：
10.1158/1078-0432.ccr-13-3227
发表时间：
2014-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cook KL;Wärri A;Soto-Pantoja DR;Clarke PA;Cruz MI;Zwart A;Clarke R
通讯作者：
Clarke R
影响因子：
5.2
作者：
Kim, Hyeon Jun;Lee, Seung Gee;Kim, Jong-Min
通讯作者：
Kim, Jong-Min
DOI：
10.1073/pnas.0905718106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Creighton, Chad J.;Li, Xiaoxian;Chang, Jenny C.
通讯作者：
Chang, Jenny C.
影响因子：
4.3
作者：
Cufi, Silvia;Vazquez-Martin, Alejandro;Menendez, Javier A.
通讯作者：
Menendez, Javier A.