TRIAL COMPARING ADJUVANT CLODRONATE THERAPY VERSUS PLACEBO IN BREAST CANCER

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项第三阶段的前瞻性随机、双盲、安慰剂对照试验将评估第二代双磷酸盐氯屈膦酸盐在早期乳腺癌妇女中的价值。要有资格参加这项试验，女性必须接受过全乳房切除或肿块切除加腋窝清扫或前哨淋巴结活检。对于接受前哨淋巴结活检的患者，只有那些参与NSABP B-32的患者才有资格。如果前哨淋巴结活检是在B-32方案之外进行的，则需要完成腋窝清扫。患者将根据年龄、结节状态以及ER和/或PGR受体状态进行分层。患者必须没有转移性疾病的证据。辅助化疗和/或他莫昔芬的给药将由研究人员酌情决定，并将记录在研究记录中。确切的方案、剂量和持续时间将由研究人员自行决定。在最初的五年中，患者将每六个月接受一次随访，此后每12个月进行一次。为了充分确定对骨和所有其他潜在复发部位的治疗效果，将跟踪每个患者的复发部位，直到发生骨转移和非骨转移(包括内脏部位、软组织部位和/或局部/区域复发部位)。患者将继续他们指定的治疗三年或直到第一次明确的骨转移，即使患者以前有过非骨骼复发或第二次原发癌症。这项试验的主要目的是：1)确定每天服用1600毫克的氯屈膦酸盐，无论是单独服用，还是在辅助化疗和/或激素治疗的同时服用3年，是否会提高无病存活率；2)评估辅助性克屈膦酸盐是否能减少骨转移、骨相关发病率、非骨转移以及改善无复发存活期和总存活率；以及3)研究血清骨转换标志物作为骨转移发展的预测因素的相关性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This phase III prospective randomized, double-blind, placebo-controlled trial will evaluate the worth of clodronate, a second-generation biphosphonate, in women with early-stage breast cancer. To qualify for this trial, women must have undergone either a total mastectomy or a lumpectomy with either an axillary dissection or sentinel node biopsy. For patients undergoing sentinel node biopsy, only those participating in NSABP B-32 will be eligible. If sentinel node biopsy is performed outside the B-32 protocol, completion of axillary dissection is required. Patients will be stratified according to age, nodal status and ER and/or PgR receptor status. Patients must have no evidence of metastatic disease. The administration of adjuvant chemotherapy and/or tamoxifen will be at the discretion of the investigator and will be documented in the study record. The exact regimen, dose and duration wil be at the discretion of the investigator. Patients will be followed every six months for the first five years and every 12 months thereafter. In order to fully determine treatment effects on both bone and all other potential sites of recurrence, each patient will be followed for sites of recurrence until the development of both bone and non-bone metastasis (this includes visceral sites, soft tissue sites and/or local/regional recurrence sites) have occurred. Patients will continue their assigned therapy for three years or until first definite bone metastasis, even if the patient has had a prior non-skeletal recurrence or second primary cancer. The primary aims of this trial are: 1) to determine whether 1,600 mg/day of clodronate, given for three years, either alone or in addition to adjuvant chemotherapy and/or hormonal therapy will improve disease-free survival; 2) to evaluate whether adjuvant clodronate results in a reduction in skeletal metastases, skeletal-related morbidity, non-skeletal metastases, and an improvement in relapse-free survival and overall survival; and 3) to investigate the relevance of serum markers of bone turnover as a prognostic factor for the development of bone metastases.