CLINICAL TRIAL: INDIVIDUALIZED TX OF BREAST CANCER BASED ON TUMOR MOLECULAR CHAR

临床试验：基于肿瘤分子碳的乳腺癌个体化治疗

• 批准号: 7718400
• 负责人: Silvia C. Formenti
• 金额: $ 0.22万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718400
• 关键词: Aftercare; Arts; Biopsy; Characteristics; Chemotherapy-Oncologic Procedure; Chest wall structure; Clinical Trials; Communities; Complement; Computer Retrieval of Information on Scientific Projects Database; Core Biopsy; Disease; Disease-Free Survival; Effectiveness; Excision; Fluorouracil; Funding; General Population; Goals; Grant; Healthcare; Individual; Institution; Measures; Molecular; Outcome; Paclitaxel; Patients; Performance; Pharmaceutical Preparations; Population; Predictive Factor; Protocols documentation; Quality of life; Radiation; Radiation therapy; Research; Research Personnel; Resources; Skin; Sorting - Cell Movement; Source; Staging; Surrogate Endpoint; TP53 gene; Taxane Compound; Testing; Tissues; Trastuzumab; Treatment Protocols; Underserved Population; United States National Institutes of Health; base; cancer therapy; capecitabine; chemotherapy; expectation; experience; improved; killings; malignant breast neoplasm; response; taxane; tumor

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. Locally advanced breast cancer (LABC), defined as a tumor >5 cm or one which shows chest wall or skin involvement, has become rare in the general population of individuals with reasonable health care. However, in the under-served population it remains relatively common. Current therapy consists of pre-operative biopsy then pre-operative chemotherapy followed by excision of the tumor. This allows the tumor-specific markers to be discovered and the effectiveness of the chemotherapy regimen to be assessed. Experience suggests that the pathological response of the tumor to the primary chemotherapy can be used as a surrogate endpoint for survival: for a group, the "better" the initial treatment the better the survival measures of overall survival (OS) and disease-free survival (DFS). Adding radiation as part of the initial treatment helps improve the response to initial treatment locally to complement the effects of chemotherapy with 5-FU to kill micrometastatic disease elsewhere in the body, as these investigators have shown previously. Correlation with pretreatment biopsy showed that p53 over-expression was the only independent predictive factor for pathological response consistent with the poor performance of 5-FU with such disease. In the case of tissue that over-expresses p53, taxanes are a better choice. Treatment of tumors positive for HER-2/neu is improved with the addition of Trastuzumab to the regimen. These observations led to the current study. With the goal of maximizing the response to the initial treatment, and therefore of maximizing measures of survival, patients will be sorted into 4 groups depending on whether their tumors are positive or not for p53 and positive or not for HER-2/neu. p53-negative tumors will be treated with Capecitabine and p53-positive with Paclitaxel. HER-2/neu-positive tumors will be treated with Trastuzumab. All patients will receive radiotherapy. This study brings the state-of-the-art in anti-cancer treatment to a group of people who are typically underserved within the community. The investigators have developed this protocol fully to employ earlier studies of similar populations with this disease and stage. The study will test the feasibility of managing treatments targeting specific tumor characteristics and will allow a comparison with the results of earlier trials where targeting was not employed. Secondary objectives will be to accumulate core biopsies before and after treatment and to look at quality of life. However, this is a trial where targeted treatment is being used with drugs that are expected to make a difference. This makes this trial unusual and valuable. Thus far, patient outcomes have conformed with expectations.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 局部晚期乳腺癌(LABC)，定义为5厘米的肿瘤或显示胸壁或皮肤受累的肿瘤，在拥有合理医疗保健的普通人群中已变得罕见。然而，在服务不足的人群中，这种情况仍然相对常见。目前的治疗方法包括术前活组织检查、术前化疗、肿瘤切除。这使得发现肿瘤特异性标志物和评估化疗方案的有效性成为可能。经验表明，肿瘤对初级化疗的病理反应可以作为生存的替代终点：对于一个组来说，初始治疗越好，总体生存期(OS)和无病生存期(DFS)的生存指标就越好。将放射作为初始治疗的一部分，有助于改善对局部初始治疗的反应，以补充5-FU化疗的效果，以杀死体内其他地方的微转移疾病，这些研究人员以前已经证明过。与治疗前活检的相关性表明，P53的过度表达是唯一独立的病理反应预测因子，与5-FU对此类疾病的不良表现一致。对于过度表达P53的组织，紫杉烷是更好的选择。HER-2/neu阳性肿瘤的治疗随着曲妥珠单抗的加入而得到改善。这些观察结果导致了目前的研究。为了最大限度地提高对初始治疗的反应，从而最大限度地提高生存指标，患者将根据他们的肿瘤是否P53阳性和HER-2/neu阳性分为4组。P53阴性的肿瘤将用卡培他滨治疗，P53阳性的肿瘤将用紫杉醇治疗。HER-2/neu阳性肿瘤将用曲妥珠单抗治疗。所有患者都将接受放射治疗。这项研究将最先进的抗癌治疗带给了一群在社区中通常得不到充分服务的人。研究人员已经完全开发了这一方案，以利用早期对患有这种疾病和分期的类似人群的研究。这项研究将测试管理针对特定肿瘤特征的治疗的可行性，并将允许与早期未使用靶向的试验的结果进行比较。次要目标将是在治疗前后积累核心活组织检查，并观察生活质量。然而，这是一项试验，靶向治疗正在与有望产生效果的药物一起使用。这使得这次试验变得不同寻常和有价值。到目前为止，患者的结果符合预期。