Li Na, Jin Zi-liang, Liu Zhu-jun, Wang Jing, Li Kai
Department of Thoracic Oncology, Tianjin Cancer Hospital, Tianjin Medical. University, Lung Cancer Center of Tianjin. Tianjin 300060, China.
Zhonghua Zhong Liu Za Zhi. 2011 Dec;33(12):937-42.
To observe the correlation between long term efficacy/safety and treatment cycles of rh-endostatin (endostar) combined with TP (paclitaxel plus cisplatin/carboplatin) or NP (navelbine plus cisplatin/carboplatin) regimens in patients with advanced non-small cell lung cancer (NSCLC).
Twenty-five patients with advanced NSCLC confirmed by histopathology and/or cytology were enrolled in this study. Twenty-one patients underwent endostar combined with NP regimen and other four patients underwent endostar combined with TP regimen (all repeated 21 days) treatment. The therapeutic effects, quality of life (QOL) and adverse effects were evaluated according to RECIST criteria, Karnofsky performance scores and WHO grading of adverse effects, respectively. Our intention was to make knowledge of the therapeutic effects, median time to progression, one-year survival rate, median overall survival and adverse reactions. The amount of circulating endothelial cells (CEC) in peripheral blood was measured by flow cytometry.
All the 25 patients were evaluable for efficacy and safety. They were comprised of 5 cases of PR, 14 cases of SD and 6 cases of PD. Of the 25 cases, RR was obtained in 5 cases (20.0%), CBR in 19 cases (76.0%), mTTP was 8 months and mOS was 19 months. Of the 14 patients with short treatment cycles (< 4), PR was obtained in 2 cases, SD in 6 cases and PD in 6 cases, RR was 14.3%. Of the 8 patients who obtained PR or SD, the median TTP was 6 months and median overall survival was 18 months. Of the 11 patients with long treatment cycles (≥ 4), PR was obtained in 3 cases, SD in 8 cases, RR was 27.3%, mTTP was 17 months and mOS was 26 months. After treatment, the amount of activated CECs was increased by (293 ± 12)/10(5) in patients with short treatment cycles, and decreased by (243 ± 181)/10(5) in patients with long treatment cycles. A positive correlation was found between the changes of activated CECs after therapy, time to progression (TTP) and treatment cycles (r = 0.970, P = 0.001; r = 0.829, P = 0.042, respectively). The quality of life (QOL) was improved in 12 cases (48.0%), stable in 10 cases (40.0%), and decreased in 3 cases (12.0%). Grade 3 and 4 toxicities were mainly related with chemotherapeutics, including neutropenia in 4 cases (16.0%), vomiting in 3 cases (12.0%) and arrhythmia in 1 case. No hypertension was observed. All the adverse reactions did not affect the following treatment, and there was no significant difference in incidence rate of grade 3 and 4 adverse events between the patients treated with long-term and short-term cycles.
Endostar combined with TP or NP regimen chemotherapy is effective and safe in the treatment of advanced NSCLC, especially in patients with long term treatment cycles which can effectively prolong TTP and reach long term survival, but not increase adverse events. The QOL of patients can be improved or remain stable. The changes of CECs may be used as a useful maker in predicting the efficacy of the combination treatment.
观察重组人血管内皮抑制素（恩度）联合TP（紫杉醇加顺铂/卡铂）或NP（长春瑞滨加顺铂/卡铂）方案治疗晚期非小细胞肺癌（NSCLC）患者的长期疗效/安全性与治疗周期之间的相关性。
纳入25例经组织病理学和/或细胞学确诊的晚期NSCLC患者。21例患者接受恩度联合NP方案治疗，另外4例患者接受恩度联合TP方案治疗（均每21天重复一次）。分别根据RECIST标准、卡诺夫斯基体能状态评分和世界卫生组织不良反应分级标准评估治疗效果、生活质量（QOL）和不良反应。我们旨在了解治疗效果、疾病进展时间中位数、一年生存率、总生存中位数和不良反应。采用流式细胞术检测外周血中循环内皮细胞（CEC）数量。
25例患者均可进行疗效和安全性评估。其中部分缓解（PR）5例，疾病稳定（SD）14例，疾病进展（PD）6例。25例患者中，缓解率（RR）为5例（20.0%），临床受益率（CBR）为19例（76.0%），疾病进展时间中位数（mTTP）为8个月，总生存中位数（mOS）为19个月。治疗周期短（<4个周期）的14例患者中，PR 2例，SD 6例，PD 6例，RR为14.3%。获得PR或SD的8例患者中，TTP中位数为6个月，总生存中位数为18个月。治疗周期长（≥4个周期）的11例患者中，PR 3例，SD 8例，RR为27.3%，mTTP为17个月，mOS为26个月。治疗后，治疗周期短的患者活化CEC数量增加（293±12）/10⁵，治疗周期长的患者活化CEC数量减少（243±181）/10⁵。治疗后活化CEC变化与疾病进展时间（TTP）和治疗周期之间呈正相关（r分别为0.970，P = 0.001；r为0.829，P = 0.042）。生活质量（QOL）改善12例（48.0%），稳定10例（40.0%），下降3例（12.0%）。3级和4级毒性主要与化疗药物有关，包括中性粒细胞减少4例（16.0%），呕吐3例（12.0%），心律失常1例。未观察到高血压。所有不良反应均未影响后续治疗，长期和短期治疗周期患者3级和4级不良事件发生率无显著差异。
恩度联合TP或NP方案化疗治疗晚期NSCLC有效且安全，尤其是治疗周期长的患者，可有效延长TTP并实现长期生存，且不增加不良事件。患者的QOL可得到改善或保持稳定。CEC的变化可能作为预测联合治疗疗效的有用指标。
