Hu Xichun, Zhang Jian, Xu Binghe, Jiang Zefei, Ragaz Joseph, Tong Zhongsheng, Zhang Qingyuan, Wang Xiaojia, Feng Jifeng, Pang Danmei, Fan Minhao, Li Jin, Wang Biyun, Wang Zhonghua, Zhang Qunling, Sun Si, Liao Chunmei
Department of Medical Oncology, Fudan University, Shanghai Cancer Center, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Int J Cancer. 2014 Oct 15;135(8):1961-9. doi: 10.1002/ijc.28829. Epub 2014 Mar 20.
Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS.
阿帕替尼是一种口服的、高效的靶向血管内皮生长因子受体2（VEGFR2）的酪氨酸激酶抑制剂。I期研究显示推荐剂量为750毫克/天，具有显著的抗肿瘤活性。本II期研究旨在评估阿帕替尼单药治疗中国转移性三阴性乳腺癌（mTNBC）的经大量治疗患者的疗效和安全性的最佳剂量水平。IIa期首先在25例先前接受过蒽环类药物和/或紫杉烷治疗的患者中进行。所有患者接受阿帕替尼750毫克/天口服，每4周为一个周期。随后，启动了一项59例患者的IIb期研究，终点为无进展生存期（PFS）。IIb期的药物剂量根据IIa期研究的安全性、耐受性和疗效确定。由于IIa期750毫克剂量相关的毒性，IIb期阿帕替尼的推荐初始剂量为500毫克/天。在IIb期，3/4级血液学毒性为血小板减少（13.6%）、白细胞减少（6.8%）、中性粒细胞减少（3.4%）和贫血（1.7%）。最常见的3/4级非血液学毒性为手足综合征、蛋白尿、高血压和谷丙转氨酶升高。在56例可评估患者中，总缓解率和临床获益率（CBR）分别为10.7%和25.0%。中位PFS和总生存期分别为3.3（95%CI 1.7 - 5.0）个月和10.6（95%CI 5.6 - 15.7）个月。我们的结果表明，对于经大量治疗、有可测量部分缓解率和PFS的mTNBC患者，推荐起始剂量为500毫克而非750毫克的阿帕替尼。
