Powles Trevor, Paterson Sandy, Kanis John A, McCloskey Eugene, Ashley Sue, Tidy Alwynne, Rosenqvist Kirsi, Smith Ian, Ottestad Lars, Legault Sandra, Pajunen Marjo, Nevantaus Auli, Männistö Esa, Suovuori Anne, Atula Sari, Nevalainen Jaakko, Pylkkänen Liisa
Royal Marsden National Health Service Trust, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK.
J Clin Oncol. 2002 Aug 1;20(15):3219-24. doi: 10.1200/JCO.2002.11.080.
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.
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.
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 [CI], 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% CI, 0.22 to 0.86; P =.016). The occurrence of nonosseous 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.
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.
骨转移的发生依赖于肿瘤诱导的破骨细胞性骨吸收，而抗骨溶解双膦酸盐氯膦酸盐可能会抑制这种吸收。给予原发性乳腺癌患者氯膦酸盐，可能会降低随后骨转移的发生率。
这项双盲、多中心试验在1989年至1995年间纳入了1069例可评估的可手术乳腺癌患者。所有患者均根据需要接受手术、放疗、化疗和他莫昔芬治疗。患者被随机分配，从初次治疗的6个月内开始，口服氯膦酸盐1600mg/d或安慰剂，为期2年。主要终点是在用药期间和整个随访期（中位随访时间为2007天）内按意向性分析的骨复发情况。次要终点是其他部位的复发、死亡率和毒性。
在整个随访期内，骨转移的发生率有非显著性降低（氯膦酸盐组，n = 63；安慰剂组，n = 80；风险比[HR]，0.77；95%置信区间[CI]，0.56至1.08；P = 0.127）。在用药期间，骨转移的发生率有显著性降低（氯膦酸盐组，n = 12；安慰剂组，n = 28；HR，0.44；95%CI，0.22至0.86；P = 0.016）。非骨转移的发生率相似（氯膦酸盐组，n = 112；安慰剂组，n = 128；P = 0.257），但在整个随访期内死亡率有显著性降低（氯膦酸盐组，n = 98；安慰剂组，n = 129；P = 0.047）。
给予原发性可手术乳腺癌患者氯膦酸盐，可能会降低骨转移的发生率，尽管这种降低仅在用药期间有显著性。死亡率有显著性降低。
