Isaacs Claudine, Slack Rebecca, Gehan Edmund, Ballen Karen, Boccia Ralph, Areman Ellen, Kramer Ruthie, Hayes Daniel F, Herscowitz Herbert, Lippman Marc
Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Washington, DC, 20057, USA.
Breast Cancer Res Treat. 2005 Sep;93(2):125-34. doi: 10.1007/s10549-005-4445-y.
This Phase III randomized multicenter trial compared progression-free (PFS) and overall survival (OS) for autologous peripheral blood stem cell (aPBSC) transplantation with or without immunotherapy in high-risk breast cancer patients.
Eligible patients had American Joint Committee on Cancer (AJCC) 5th Edition Stage II/IIIA with > or = 4 axillary nodes, Stage IIIB, or chemotherapy-sensitive or stable Stage IV disease. Following treatment with cyclophosphamide, thiotepa and carboplatin (STAMP V), patients were randomized to aPBSC transplant with or without immunotherapy. Patients on immunotherapy received cells that were incubated in interleukin-2 (IL-2) for 24 h followed by parenteral IL-2 for 5 days then 2 days of rest for 4 weeks.
Fifty-nine patients were treated (35 Stage II/IIIA; 13 Stage IIIB; 11 Stage IV), 30 patients were randomized to immunotherapy and 29 patients to no immunotherapy. Neutrophils engrafted a median of 10 days post-transplant in both groups. The median times to platelet engraftment were 9 and 10 days after transplant in the no-immunotherapy and immunotherapy groups, respectively (p = 0.03). There was no statistical evidence (p = 0.61) of a difference in progression-free and surviving (PFS) at 3 years for patients receiving immunotherapy (53%) compared with no immunotherapy (48%). There was some evidence of superiority in overall survival (OS) at 3 years for patients receiving immunotherapy (83%) compared with no immunotherapy (69%), but the difference between survival curves was not statistically significant (p = 0.08). Also, there was some evidence that patients developing acute graft versus host disease (aGVHD) had superior PFS (p = 0.02) but not OS (p = 0.19) than patients not developing aGVHD. Toxicities were transient and similar between groups, with no treatment-related deaths.
This phase III study of high-risk breast cancer patients randomized to immunotherapy or no immunotherapy demonstrated that a well-tolerated immunotherapy regimen added to aPBSC transplant did not improve PFS, but there was some improvement in OS, but not by an amount that was statistically significant (p = 0.08).
本III期随机多中心试验比较了高危乳腺癌患者接受自体外周血干细胞（aPBSC）移植加或不加免疫治疗的无进展生存期（PFS）和总生存期（OS）。
符合条件的患者为美国癌症联合委员会（AJCC）第5版II/IIIA期且腋窝淋巴结≥4个、IIIB期或化疗敏感或病情稳定的IV期疾病患者。在接受环磷酰胺、噻替派和卡铂（STAMP V）治疗后，患者被随机分为接受或不接受免疫治疗的aPBSC移植组。接受免疫治疗的患者所接受的细胞在白细胞介素-2（IL-2）中孵育24小时，然后接受肠外IL-2治疗5天，接着休息2天，共4周。
共治疗59例患者（35例II/IIIA期；13例IIIB期；11例IV期），30例患者被随机分配接受免疫治疗，29例患者不接受免疫治疗。两组中性粒细胞在移植后中位10天植入。在未接受免疫治疗组和免疫治疗组中，血小板植入的中位时间分别为移植后9天和10天（p = 0.03）。接受免疫治疗的患者（53%）与未接受免疫治疗的患者（48%）相比，3年时无进展生存期（PFS）无统计学差异（p = 0.61）。有一些证据表明，接受免疫治疗的患者（83%）与未接受免疫治疗的患者（69%）相比，3年总生存期（OS）有优势，但生存曲线之间的差异无统计学意义（p = 0.08）。此外，有一些证据表明，发生急性移植物抗宿主病（aGVHD）的患者与未发生aGVHD的患者相比，PFS更优（p = 0.02），但OS无差异（p = 0.19）。毒性反应是短暂的，两组相似，且无治疗相关差异。
这项针对高危乳腺癌患者随机分为免疫治疗组或非免疫治疗组的III期研究表明，在aPBSC移植基础上加用耐受性良好的免疫治疗方案并未改善PFS，但OS有一定改善，但未达到统计学显著水平（p = 0.08）。
