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背景:氯膦酸二钠(固令~)能够通过抑制肿瘤诱导的破骨细胞对骨的溶解,减少骨转移的发生率。方法:在1989-2000年,该随机双盲、安慰剂对照的多中心临床研究观察了1069位Ⅰ-Ⅲ期的乳腺癌患者,并评价了口服氯膦酸二钠的有效性和安全性。在早期治疗(手术,放疗,服用他莫西芬)的6个月内开始,患者服用氯膦酸二钠(1600mg/天)或安慰剂2年。以在5年研究期间第一次骨转移发生时间作为治疗的首要终点,二级终点是总体生存率。用非分层的时序检验对风险比(HR)进行统计分析。结果:各组间患者的人口统计学参数相似。与安慰剂组比较,在2年药物治疗后,口服氯膦酸二钠降低全部患者骨转移风险达45%(HR=0.546,P=0.031),5年的研究阶段后骨转移风险降低31%(HR=0.692,P=0.043)(见图1)。与安慰剂相比,口服氯膦酸二钠能显著提高总体生存率(死亡率下降23%:HR=0.768,P=0.048)和Ⅱ/Ⅲ期患者生存率(死亡率下降26%:HR=0.743,P=0.041)。患者对口服氯膦酸二钠有良好的耐受性,轻度到中度的腹泻是报道最频繁的药物不良反应。结论:对于早期乳腺癌患者,口服氯膦酸二钠能显著地降低药物治疗期和研究期间骨转移的发生率,并在10.5年的随访中显著的提高了总体生存率和Ⅱ/Ⅲ期患者生存率。
BACKGROUND: Disodium clodronate (Doxorhizobium) can reduce the incidence of bone metastasis by inhibiting tumor-induced osteolysis of osteoclasts. METHODS: In a randomized, double-blind, placebo-controlled multicenter clinical study of 1,069 breast cancer patients with stage I-III in 1989-2000, the efficacy and safety of oral clodronate were evaluated. Commencing within 6 months of early treatment (surgery, radiotherapy, tamoxifen), patients took clodronate (1600 mg / day) or placebo for 2 years. As the primary end point of treatment, the first bone metastasis occurred during the 5-year study, the secondary endpoint was overall survival. The risk ratio (HR) was statistically analyzed using a non-stratified time series test. Results: The demographic parameters of patients in each group were similar. Oral oral clodronate reduced the risk of bone metastases by 45% in all patients (HR = 0.546, P = 0.031) after 2 years of drug treatment compared with placebo, with a 31% reduction in the risk of bone metastases after a 5-year study period (HR = 0.692, P = 0.043) (see Figure 1). Compared with placebo, oral clodronate significantly increased overall survival (23% reduction in mortality: HR = 0.768, P = 0.048) and survival in patients with stage II / III (mortality decreased 26%: HR = 0.743, P = 0.041). Patients with oral resistance to oral clodronate have good tolerance, mild to moderate diarrhea is the most frequently reported adverse drug reactions. CONCLUSIONS: Oral oral CPD can significantly reduce the incidence of bone metastases during the drug treatment and study period in patients with early-stage breast cancer and significantly improve overall survival at the 10.5-year follow-up and stage II / III patients Survival rate.