目的 評(píng)價(jià)聚乙二醇重組人血管內(nèi)皮抑制素注射液（PEGylated recombinant human endostatin solution for injection，M2ES）在非小細(xì)胞肺癌患者中聯(lián)合紫杉醇、卡鉑化療（TC方案）多劑量給藥的耐受性和安全性。方法 23例經(jīng)病理確診的晚期非小細(xì)胞肺癌患者按入組標(biāo)準(zhǔn)進(jìn)入本研究。M2ES共包括4個(gè)劑量組：7.5、10、12.5、15 mg/m2，每個(gè)劑量組至少含3例非小細(xì)胞肺癌患者；第1天按175（±20%）mg/m2給予紫杉醇，第2天按AUC=（5±0.5）mg/(mL?min)給予卡鉑，M2ES按給藥劑量組設(shè)定的劑量于第3、10、17天給藥，21 d為1個(gè)周期，共2個(gè)周期。觀察治療期間患者的耐受性和安全性，治療結(jié)束計(jì)算客觀有效率和疾病控制率。結(jié)果 M2ES聯(lián)合TC方案最常見(jiàn)的不良反應(yīng)是白細(xì)胞下降82.6%、心電圖異常34.8%、惡心21.7%。劑量限制性毒性見(jiàn)于15 mg/m2劑量組，表現(xiàn)為1例IV度皮疹、1例III度黃疸和IV度轉(zhuǎn)氨酶異常。M2ES最大耐受劑量（MTD）為15 mg/m2，推薦Ⅱ期臨床試驗(yàn)劑量為12.5 mg/m2。根據(jù)RECIST標(biāo)準(zhǔn)評(píng)價(jià)腫瘤緩解程度，治療結(jié)束時(shí)13例患者病情穩(wěn)定，2例患者部分緩解，臨床有效率為13.3%，臨床受益率為100%。結(jié)論 M2ES與TC聯(lián)合并不明顯增加化療的不良反應(yīng)，M2ES的MTD為15 mg/m2, 推薦Ⅱ期臨床試驗(yàn)劑量為12.5 mg/m2。

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.