恩度与化疗联合治疗多种晚期恶性肿瘤的临床观察

Endostar combined with chemotherapy on the multiple kinds of advanced malignancies

目的:前瞻性观察抗肿瘤新药重组人血管内皮抑素注射液(YH-16,恩度)联合化疗治疗多种晚期恶性肿瘤的有效性和安全性。方法:经病理组织学或细胞学检查确诊的Ⅳ期恶性肿瘤患者36例,其中非小细胞肺癌(NSCLC)9例,其他肿瘤27例(大肠癌7例,头颈部鳞癌5例,小细胞肺癌、食管癌、肾癌、胰腺癌和胆管癌各2例,肾盂癌、原发性肝癌、卵巢癌、纵隔卵黄囊瘤和腹膜转移性腺癌各1例),接受恩度联合化疗的方案治疗。其中恩度15mg,加入生理盐水500ml中匀速缓慢静脉滴注,第1～14天连续给药,间歇7天重复;同时联合既往未使用的或与既往治疗无交叉耐药的化疗药物。每21天为1个周期。按照RECIST标准评价近期疗效,参照Karnofsky评分(KPS)变化评价生活质量(QOL),按照NCICTC3.0版标准评价毒性反应。用药1周期即可评价毒性,2周期后方可评价疗效。结果:全组36例患者中,有30例患者可以评价客观疗效,36例均可进行安全性评价。总共完成的周期数为83个周期,平均2.3个周期。30例可评价病例中,获得PR4例,SD17例,PD9例,即客观有效率(RR)为13.3%(4/30),疾病控制率(DCR)为70.0%(21/30);而生活质量改善者有11例(36.7%),稳定者13例(43.3%),仅6例(20.0%)下降。G3/4级毒性主要与化疗药物有关,包括1例(2.7%)白细胞下降、3例(8.3%)血小板下降、1例(2.7%)恶心/呕吐以及1例(2.7%)腹泻。结论:恩度与化疗药物联合使用可以改善和稳定多种晚期恶性肿瘤患者的生活质量,与部分化疗药物具有协同作用,其毒性低,安全性好,值得临床上推广应用和进一步深入观察。

Objective：To observe prospectively and systematically the efficacy and safety of rh-endostatin injection （YH-16, Endostar）, a new molecular targeted anti-tumor agent, combined with the chemotherapy on the multiple kind of advanced malignancies. Methods：Endostar combined with chemotherapy were administrated to 36 malignant cases of stage IV （including 9 cases with non-small cell lung cancer , 27cases with other cancers）confirmed by histopathology or cytopathology. 15mg endostar solved in 500ml of normal saline was slow intravenously dropped from day 1 to day 14, repeated after 7 days later. The chemotherapy agents which was not used before or not cross-resistant to pre-chemotherapeutic agents were selected to be given simultaneously. The regimen was repeat- ed every 21days. The efficacy was evaluated strictly after 2 cycles according to RECIST criteria,and quality of life （QOL） was evaluated according to Karnofsky scores. Otherwise safety was evaluated after 1 cycle according to NCI CTC 3.0 version criteria. Results： Thirty cases were evaluable for efficacy among the total 36 cases that were capable of safety evaluation. Totally 83 cycles were completed and mean cycle was 2. 3. Among 30 evaluable cases, there were 4 cases achieved PR, 17 cases of SD, and 9 cases of PD. The objective response rate （RR） was 13.3% （4/30） and disease control rate （DCR） was 70. 0% （21/30）. The quality of life （QOL） were improved on 11 cases （36.7%）, stabled on 13 cases （43. 3% ） , and decreased on 8 cases （20. 0% ）. The occurrence rates of G3/4 toxicities were low, including neutropenia （ 1/36,2. 7% ）, thrombocytopenia （3/36, 8. 3% ）, nausea/vomiting （ 1/36,2. 7% ）, and diarrhea （1/36,2. 7% ）. These toxicities were mainly related with the chemotherapy agents. Conclusion：The QOL of patients with multiple kinds of advanced malignancies may be improved by endostar combined with the related chemotherapy. Maybe there have synergetic effects of endostar with some of cytotoxic agents. It is worthy of clinical generalization and further clinical observation.