聚乙二醇重组人血管内皮抑制素注射液联合TC方案治疗晚期非小细胞肺癌的单中心、开放性Ⅰ期临床安全性研究

目的 评价聚乙二醇重组人血管内皮抑制素注射液(PEGylated recombinant human endostatin solution for injection,M2ES)在非小细胞肺癌患者中联合紫杉醇、卡铂化疗(TC方案)多剂量给药的耐受性和安全性.方法 23例经病理确诊的晚期非小细胞肺癌患者按入组标准进入本研究.M2ES共包括4个剂量组:7.5、10、12.5、15 mg/m2,每个剂量组至少含3例非小细胞肺癌患者；第1天按175(±20％) mg/m2给予紫杉醇,第2天按AUC=(5±0.5) mg/(mL·min)给予卡铂,M2ES按给药剂量组设定的剂量于第3、10、17天给药,21d为1个周期,共2个周期.观察治疗期间患者的耐受性和安全性,治疗结束计算客观有效率和疾病控制率.结果 M2ES联合TC方案最常见的不良反应是白细胞下降82.6％、心电图异常34.8％、恶心21.7％.剂量限制性毒性见于15 mg/m2剂量组,表现为1例Ⅳ度皮疹、1例Ⅲ度黄疸和Ⅳ度转氨酶异常.M2ES最大耐受剂量(MTD)为15 mg/m2,推荐Ⅱ期临床试验剂量为12.5 mg/m2.根据RECIST标准评价肿瘤缓解程度,治疗结束时13例患者病情稳定,2例患者部分缓解,临床有效率为13.3％,临床受益率为100％.结论 M2ES与TC联合并不明显增加化疗的不良反应,M2ES的MTD为15 mg/m2,推荐Ⅱ期临床试验剂量为12.5 mg/m2.

Safety assessment of PEGylated recombinant human endostatin solution for injection combined with TC chemotherapy in phase I clinical studyon advanced non-small cell lung cancer

Objective To evaluate the tolerance and safety of PEGylated recombinant human endostatin solution for injection (M2ES) in patients with non-small cell lung cancer (NSCLC) by paclitaxel, carboplatin chemotherapy (TC regimen). Methods Cases (23) of patients with advanced NSCLC according to pathological diagnosis were carried into the study. M2ES consisted of four groups: 7.5, 10, 12.5, and 15 mg/m2, and each dosage group contained at least three cases of NSCLC patients. On the first day, the patients were administered with paclitaxel, 175(± 20%) mg/m2, and on the second day, they were administered with carboplatin at AUC=(5 ± 0.5) mg/(mL?min). They were administered with M2ES according to dosages which were set up on the 3, 10, 17 days of administration. The course of treatment was 21 d, lasted for 2 courses. The tolerance and safety of patients were observed, at the same time, the treatment response rate and the clinical benefit rate were calculated. Results The most common adverse reactions were leucopenia (82.6%), ECG abnormalities (34.8%), and nausea (21.7%). Dose-limiting toxicity appeared in the 15 mg/m2 dosage group, and the performance included one patient with IV-degree rash, one patient with III-degree jaundice and IV-degree transaminase abnormalities. The maximum-tolerated dose (MTD) of M2ES was 15 mg/m2. The recommended dosage for phase II clinical trial was 12.5 mg/m2. According to RECIST standard to evaluate tumor remission rate, at the end of the treatment, 13 cases of patients were with stable disease, and 2 patients were with partial remission. The clinical effective rate was 13.3%, and the clinical benefit rate was 100%. Conclusion The combination therapy of M2ES and TC regimen can be tolerated in advanced NSCLC patients. The MTD of M2ES is 15 mg/m2. The recommended dose for phase II clinical trial is 12.5 mg/m2.