晚期非小细胞肺癌患者吉西他滨血药浓度与临床疗效及不良反应相关性研究

目的：通过液质联用（LC-MS）技术测定非小细胞肺癌（non-small cell lung cancer，NSCLC）患者吉西他滨血药浓度，探讨吉西他滨血药浓度与临床疗效及不良反应的相关性。方法：入组某院化疗病区确诊为非小细胞肺癌，并接受吉西他滨联合顺铂方案化疗的患者，于输注吉西他滨完后5 min取血，采用LC-MS测定吉西他滨血药浓度，每两周期评估近期疗效，收集不良反应信息，比较高血药浓度组和低血药浓度组的临床疗效、不良反应差异，探讨两者之间相关性。结果：53例患者吉西他滨峰浓度范围为：1.58~28.70 μg·mL^-1，均值（14.37±8.63）μg·mL^-1，其中>15 μg·mL^-1组28例，≤15 μg·mL^-1组25例。>15 μg·mL^-1组客观缓解率（ORR）、临床获益率（CBR）显著高于≤15 μg·mL^-1组（P<0.05）；>15 μg·mL^-1组白细胞降低、中性粒细胞降低、血小板降低、Ⅲ~Ⅳ级胃肠道反应发生率显著高于≤15 μg·mL^-1组（P<0.05），两组血红蛋白降低、肝肾功能损害、过敏反应及皮疹等发生率差异无显著性（P>0.05）。结论：NSCLC患者吉西他滨峰浓度与临床疗效及不良反应具有相关性，高峰浓度能提高患者治疗的临床疗效，但增加了白细胞减少、粒细胞减少和血小板减少及Ⅲ~Ⅳ级胃肠道反应发生率。

The correlation between the plasma concentration of gemcitabine and clinical efficacy and adverse reactions in patients with advanced NSCLC

OBJECTIVE To determine the plasma concentration of gemcitabine in patients with non-small cell lung cancer (NSCLC) by liquid chromatography-mass spectrometry (LC-MS) and explore the correlation between plasma concentration of gemcitabine and clinical efficacy and adverse reactions.METHODS The patients who were diagnosed as non-small cell lung cancer in the chemotherapy ward of our hospital and received gemcitabine plus cisplatin chemotherapy were enrolled in this study. Plasma concentrations of gemcitabine was determined by liquid chromatography-mass spectrometry (LC-MS). The adverse reaction and short-term clinical efficacy were evaluated every 2 cycles. The adverse reaction information was collected. The clinical efficacy and adverse reaction differences between the high plasma concentration group and the low plasma concentration group were compared to explore the correlation between the two groups.RESULTS The peak concentration of gemcitabine in 53 patients ranged from 1.58 to 28.70 μg·mL^-1, with a mean of (14.37 ±8.63) μg·mL^-1, including 28 patients in the >15 μg·mL^-1 group and 25 patients in the ≤ 15 μg·mL^-1 group objective response rate (ORR) and clinical benefit rate (CBR) in >15 μg·mL^-1 group were significantly higher than those in ≤ 15 μg·mL^-1 group (P<0.05); the incidences of leukopenia, neutropenia, thrombocytopenia and gastrointestinal reactions grade Ⅲ-Ⅳ in >15 μg·mL^-1 group were significantly higher than those in ≤ 15 μg·mL^-1 group (P<0.05). There was no significant difference in the incidence of hemoglobin decrease, liver and kidney function damage, allergic reaction and rash between the two groups (P>0.05).CONCLUSION Peak concentration of gemcitabine in NSCLC patients is correlated with clinical efficacy and adverse reactions. Peak concentration can improve the clinical efficacy of treatment in patients with NSCLC, but increase the incidence of leukopenia, granulocytopenia and thrombocytopenia and gastrointestinal reactions grade Ⅲ-Ⅳ.