DOSE-INTENSE CHEMOTHERAPY AND STEM CELL RESCUE IN THE TREATMENT OF INFLAMMATORY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是评估一种治疗方法，包括化疗和手术切除癌症，然后再进行额外的化疗，然后进行两个治疗周期的高剂量治疗，并重新输注患者自身的骨髓来源细胞。炎症性乳腺癌，在常规治疗时，有很高的复发可能性。高剂量联合化疗可能改善患者的这一结果，目前正在研究一种新的药物和剂量组合。为了减少与高剂量化疗相关的潜在副作用，随后将进行干细胞抢救（将患者自身的骨髓来源细胞重新注入患者体内的过程）。年龄在18-65岁之间，诊断为IIIB期乳腺癌的患者，在诊断后6个月内至少有以下临床特征之一的患者将被纳入研究：炎症，红斑，疼痛或过敏，水肿（橘皮），皮肤增厚。病人在其他方面必须身体健康。如果患者之前接受过不超过一个周期的化疗，并且没有手术切除肿瘤，他们将开始使用一种叫做阿霉素的药物进行化疗。然后，患者将接受第二种药物紫杉醇，然后通过手术切除乳腺癌。所有患者将在96小时内通过静脉导管接受紫杉醇治疗。将给予粒细胞集落刺激因子（G-CSF）以增加血液循环中循环骨髓细胞的数量。接下来，患者将接受外周血干细胞（PBSC）采集。这个过程包括血液循环，通过一台机器将血液分离成不同的成分，并将除白细胞外的所有成分送回病人体内。患者将入院接受第一个周期的大剂量联合化疗，包括静脉输注阿霉素和环磷酰胺，第二天输注紫杉醇。随后，患者将接受先前储存的PBSC的部分再输注。在不超过7周的时间后，患者将重新入院接受第二周期的高剂量化疗，包括两种药物美法兰和顺铂，随后部分再输注先前收集的PBSC。患者从高剂量化疗恢复后将接受胸壁和淋巴结区域的放射治疗，如果肿瘤激素受体呈阳性，也将开始服用药物他莫昔芬，为期5年。治疗后，将对患者进行密切监测。

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. The purpose of this study is to evaluate a treatment consisting of chemotherapy and surgical removal of cancer followed by additional chemotherapy and then two treatment cycles of very high-dose therapy with reinfusion of patient's own bone marrow derived cells. Inflammatory breast cancer, when treated conventionally, carries a high likelihood of relapse. High doses of combination chemotherapy may improve this outcome for patients and a new combination of drugs and doses is being investigated. To reduce the potential side effects associated with high dose chemotherapy, stem cell rescue (a process in which the patient's own bone marrow derived cells are reinfused back to them) will follow. Patients between the age of 18-65 years, who are diagnosed with stage IIIB breast cancer, and who have at least one of the following clinical features within six months from the time of diagnosis will be enrolled in the study: inflammation, erythema, pain or hypersensitivity, edema (peau d'orange), thickening of skin. Patient must be in otherwise generally good health. If the patient has received no more than one prior cycle chemotherapy treatment and has not had surgical removal of their tumor, they will begin chemotherapy with a drug called doxorubicin. Then, the patient will receive a second drug, Taxol, followed by surgical removal of their breast cancer. All patients will receive Taxol through an intravenous catheter over a period of 96 hours. Granulocyte colony stimulating factor (G-CSF) will be administered to increase the number of circulating bone marrow cells in their blood circulation. Next, the patient will undergo PBSC (peripheral blood stem cell) collection. The procedure involves circulating blood through a machine that separates the blood into components and returns everything but the white blood cells back to the patient. The patient will be admitted to the hospital to receive their first cycle of high-dose combination chemotherapy, consisting of intravenous infusions of doxorubicin and cyclophosphamide, and the next day, an infusion of Taxol. Following this, the patient will receive partial reinfusions of their previously stored PBSC. After no more than a 7-week period, the patient will be readmitted to receive a second cycle of high-dose chemotherapy, consisting of two drugs melphalan and cisplatin, and following that, partial reinfusions of previously collected PBSC. The patient will receive radiation therapy to the chest wall and lymph node areas following recovery from high-dose chemotherapy, and if the tumor was hormone-receptor positive, will also start taking the drug, tamoxifen, for a period of 5 years. Following treatment, the patient will be closely monitored.