Huang Weiwei, Liu Jian, Wu Fan, Chen Kan, Li Nani, Hong Yi, Huang Cheng, Zhen Hongyu, Lin Lin
Department of Medical Oncology, Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University, the Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350014, China.
Oncotarget. 2016 May 24;7(21):31501-7. doi: 10.18632/oncotarget.8967.
The purpose of the present study was to prospectively evaluate the efficacy and safety of endostar, a recombinant product of endostatin, combined with taxane-based regimens for HER-2 negative metastatic breast cancer (MBC) patients. Women with ages between 18-70 years with histologically confirmed MBC documented as HER-2-negative were included. Endostar was administered at 7.5 mg/m2, d1-14, q21d and was continued until progressive disease, unacceptable toxicity, consent withdrawal, or completion of 24 months of endostar, whichever came first. Taxane-based chemotherapy was continued until progressive disease, unacceptable toxicity, consent withdrawal, or up to 8 cycles. The primary endpoint was overall response rate (ORR). Fifty-seven patients were recruited. The ORRs for the whole population, first-, second-, and third-line therapy or beyond were 68.4%, 79.3%, 54.5%, and 16.7%, respectively. The median PFS was 10.8 (8.0-12.1) months, yet the median OS was still not attained. For the patients receiving first-, second-, and third-line therapy or beyond, median PFS was 11.9, 7.5, and 7.4 months, respectively (P=0.048). No significant difference in median PFS between hormonal receptor-positive and -negative patients was observed. The most common drug-related grade 3-4 hematologic toxicities were neutropenia (80.7%) and leukopenia (77.2%). Six (10.5%) patients experienced febrile neutropenia. The most frequent drug-related grade 3-4 non-hematologic toxicities were liver dysfunction (10.5%) and peripheral neurotoxicity (8.8%). No treatment-related deaths were reported. We conclude that Endostar combined with taxane-based regimens may be effective and safe for the treatment of HER-2-negative MBC. However, further investigations on its long-term efficacy and toxicity are warranted.
本研究的目的是前瞻性评估重组内皮抑素恩度联合紫杉类方案治疗HER-2阴性转移性乳腺癌(MBC)患者的疗效和安全性。纳入年龄在18至70岁之间、组织学确诊为HER-2阴性的MBC女性患者。恩度按7.5 mg/m²给药,第1至14天,每21天为一周期,持续给药直至疾病进展、出现不可接受的毒性、患者撤回同意或完成24个月的恩度治疗,以先出现者为准。紫杉类化疗持续至疾病进展、出现不可接受的毒性、患者撤回同意或最多8个周期。主要终点为总缓解率(ORR)。共招募了57例患者。全人群、一线、二线、三线及以上治疗的ORR分别为68.4%、79.3%、54.5%和16.7%。中位无进展生存期(PFS)为10.8(8.0 - 12.1)个月,但中位总生存期(OS)仍未达到。接受一线、二线、三线及以上治疗的患者,中位PFS分别为11.9、7.5和7.4个月(P = 0.048)。激素受体阳性和阴性患者的中位PFS无显著差异。最常见的3 - 4级药物相关血液学毒性为中性粒细胞减少(80.7%)和白细胞减少(77.2%)。6例(10.5%)患者发生发热性中性粒细胞减少。最常见的3 - 4级药物相关非血液学毒性为肝功能损害(10.5%)和周围神经毒性(8.8%)。未报告与治疗相关的死亡病例。我们得出结论,恩度联合紫杉类方案治疗HER-2阴性MBC可能有效且安全。然而,有必要对其长期疗效和毒性进行进一步研究。