Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer
Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer
复制标题
DOI：
10.1200/jco.2002.11.080
复制
发表时间：
2002-08-01
影响因子：
45.3
通讯作者：
Pylkkänen, L
中科院分区：
文献类型：
--
作者：
Powles, T;Paterson, S;Pylkkänen, L
目的：骨转移的发生依赖于肿瘤诱导的骨吸收，而骨吸收可被抗溶骨性二膦酸盐氯膦酸盐抑制。给予原发性乳腺癌患者，氯膦酸盐可能会降低随后的骨转移的发病率。患者和方法：这个双盲，多中心试验累计1,069可评估的患者与1989年和1995年之间的可手术乳腺癌。所有患者均接受手术、放疗、化疗和他莫昔芬治疗。患者随机接受口服氯膦酸盐1，600 mg/d或安慰剂2年，从主要治疗的6个月内开始。主要终点是在药物治疗期间和总随访期间（中位随访时间为2，007天）在意向治疗基础上分析的骨复发。次要终点是其他部位复发、死亡率和毒性。结果：在整个随访期间，骨转移的发生率无显著降低（氯膦酸盐，n = 63;安慰剂，n = 80;风险比[HR]，0.77; 95%可信区间[Cl]，0.56至1.08; P =. 127）。在用药期间，骨转移的发生率显著降低（氯膦酸盐组，n = 12;安慰剂组，n = 28; HR，0.44; 95% CI，0.22 - 0.86; P = 0.016）。非骨转移的发生率相似（氯膦酸盐，n = 112;安慰剂，n = 128; P = .257），但死亡率显著降低（氯膦酸二钠，n = 98;安慰剂，n = 129; P = 0.047）。氯膦酸盐，给予原发性可手术乳腺癌患者，可能会减少骨转移的发生，尽管这种减少只在这个用药期间才有意义。死亡率显著降低。(C)2002年，美国临床肿瘤学会。
Purpose: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases.Patients and Methods: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity.Results: During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [Cl], 0.56 to 1.08; P =. 127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% Cl, 0.22 to 0.86; P = .016). The occurrence of non-osseous metastases was similar (clodronate, n = 112; placebo, n = 128; P = .257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n 129; P = .047) during the total follow-up period.Conclusion: Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality. (C) 2002 by American Society of Clinical Oncology.