Laheru Dan, Lutz Eric, Burke James, Biedrzycki Barbara, Solt Sara, Onners Beth, Tartakovsky Irena, Nemunaitis John, Le Dung, Sugar Elizabeth, Hege Kristen, Jaffee Elizabeth
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Public Health, Baltimore, Maryland 21231, USA.
Clin Cancer Res. 2008 Mar 1;14(5):1455-63. doi: 10.1158/1078-0432.CCR-07-0371.
The combination of chemotherapy and immunotherapy has not been examined in patients with advanced pancreatic cancer. We conducted a study of two granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines (CG8020/CG2505) as immunotherapy administered alone or in sequence with cyclophosphamide in patients with advanced pancreatic cancer.
This was an open-label study with two cohorts: cohort A, 30 patients administered a maximum of six doses of CG8020/CG2505 at 21-day intervals; and cohort B, 20 patients administered 250 mg/m(2) of cyclophosphamide i.v. 1 day before the same immunotherapy given as in cohort A. The primary objective was to evaluate safety and duration of immunity. Secondary objectives included time to disease progression and median overall survival.
The administration of CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity. Median survival values in cohort A and cohort B were 2.3 and 4.3 months, respectively. CD8(+) T-cell responses to HLA class I-restricted mesothelin epitopes were identified predominantly in patients treated with cyclophosphamide + CG8020/CG2505 immunotherapy.
Granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity in patients with advanced pancreatic cancer. Also, mesothelin-specific T-cell responses were detected/enhanced in some patients treated with CG8020/CG2505 immunotherapy. In addition, cyclophosphamide-modulated immunotherapy resulted in median survival in a gemcitabine-resistant population similar to chemotherapy alone. These findings support additional investigation of cyclophosphamide with CG8020/CG2505 immunotherapy in patients with advanced pancreatic cancer.
尚未在晚期胰腺癌患者中研究化疗与免疫疗法的联合应用。我们开展了一项研究，针对两种分泌粒细胞巨噬细胞集落刺激因子的胰腺癌细胞系（CG8020/CG2505），将其作为免疫疗法单独应用于晚期胰腺癌患者，或与环磷酰胺序贯应用。
这是一项开放标签研究，分为两个队列：队列A，30例患者每隔21天接受最多6剂CG8020/CG2505；队列B，20例患者在接受与队列A相同的免疫疗法前1天静脉注射250 mg/m²环磷酰胺。主要目标是评估安全性和免疫持续时间。次要目标包括疾病进展时间和中位总生存期。
单独应用CG8020/CG2505或与环磷酰胺序贯应用显示出最小的治疗相关毒性。队列A和队列B的中位生存值分别为2.3个月和4.3个月。主要在接受环磷酰胺+CG8020/CG2505免疫疗法的患者中鉴定出对HLA I类限制性间皮素表位的CD8⁺ T细胞反应。
分泌粒细胞巨噬细胞集落刺激因子的胰腺癌细胞系CG8020/CG2505单独应用或与环磷酰胺序贯应用在晚期胰腺癌患者中显示出最小的治疗相关毒性。此外，在一些接受CG8020/CG2505免疫疗法的患者中检测到/增强了间皮素特异性T细胞反应。此外，环磷酰胺调节的免疫疗法在吉西他滨耐药人群中的中位生存期与单纯化疗相似。这些发现支持对环磷酰胺联合CG8020/CG2505免疫疗法在晚期胰腺癌患者中进行进一步研究。
