唑来膦酸治疗肺癌骨转移疗效分析及骨代谢标记物变化分析

Analysis on curative effect of zoledronic acid treating bone metastasis of lung cancer and on change of biochemical bone

目的研究唑来膦酸治疗肺癌骨转移的临床疗效情况;以及研究唑来膦酸对骨代谢标记物血清碱性磷酸酶(alkaline phosphatase,ALP)的影响。方法本研究选取了福建省立医院肿瘤内科2008年9月至2012年6月收治的60例肺癌骨转移患者。唑来膦酸每4周使用1次,每次4mg,共用5次。观察指标为:在唑来膦酸治疗前及治疗7天后分别对止痛疗效及不良反应评估,在唑来膦酸治疗前及治疗4个月后分别对骨病灶疗效,骨代谢标志物ALP变化情况评估。结果通过治疗观察,治疗后患者的疼痛程度减轻,并在控制骨转移病灶上疗效确切。基线ALP水平明显高于正常;其浓度与骨转移灶程度相关,其中小于3处骨转移者ALP与大于等于3处骨转移者ALP平均值比较差异有统计学意义(P<0.05);基线ALP水平与疼痛强度中度相关,治疗4个月后ALP水平有所降低;治疗前后血肌酐水平、血钙无明显变化,治疗期间无骨相关事件发生。8例患者发生了2次可能与唑来膦酸相关的不良事件。结论在肺癌骨转移的治疗方面,使用唑来膦酸联合化疗或生物靶向治疗是有效治疗方式之一,唑来膦酸止痛方面疗效确切,并有控制骨转移病灶作用,其耐受性和安全性良好,另骨代谢标志物ALP基线水平大部分高于正常值;基线ALP浓度与骨转移程度相关;与疼痛强度中度相关;在肺癌骨转移患者中ALP在病情变化、疗效评估及预后判断等方面提供帮助.

Objective To investigate the clinical curative effect of zoledronic acid treating bone metastasis of lung cancer and to research the effect of zoledronic acid on biochemical bone markers, i.e. alkaline phosphatase （ALP）.Method This study selected 60 cases of bone metastasis of lung cancer treated by Department of Medical Oncology of Fujian Provincial Hospital from September 2008 to February 2010. These patients took zoledronic acid at 4mg/token for once in 4 weeks and 5 times in total. Pain-killer effect and adverse drug effect was evaluated respectively before and 7 days after the treatment of zoledronic acid, and effect of bone lesions and level of ALP was measured before and 4 months after the treatment of zoledronic acid. Result Through observation on treatment, the patients treated with zoledronic acid suffered less pain, with definitive effect on the control of the bone metastases lesions. The ALP level was significantly above the upper limit of normal at baseline; and its concentration was correlated to the severity of bone metastases. Statistically significant difference existed between the average ALP level of the patients with less than 3 bone metastasis and those with more than 3 bone metastasis（P〈0.05）. The ALP level at baseline was moderately correlated to the degree of pain, and it declined 4 months after the treatment. No significant difference was found between the level of serum creatinine and blood calcium before and after the treatment, and no bone-related events occurred during the treatment. However, two adverse events occurred among the 8 patients which might be associated with zoledronic acid. Conclusion Combined chemotherapy with zoledronic acid or biological target therapy is an effective treatment on bone metastasis of lung cancer. It has a definitive effect on the pain-killing and the control of the bone metastases lesions, with moderate safeness and drug tolerance. The ALP level is mostly above the upper limit of normal at baseline. The ALP level at baseline correlates to the extent of bone metastases and pain intensity moderately. Serum ALP has certain referable value for the evaluation of disease evolution, drug effect and prognosis among patients with bone metastasis of lung cancer.