Dai Wangshu, Qiu Xin, Lu Changchang, Zou Zhengyun, Sha Huizi, Kong Weiwei, Liu Baorui, Du Juan
The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
The Cadre Health Care Ward, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Front Oncol. 2021 Oct 13;11:693386. doi: 10.3389/fonc.2021.693386. eCollection 2021.
To date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the past few years, the interest in immunological anticancer therapy rises sharply. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen.
Nab-paclitaxel (125 mg/m) and gemcitabine (1000 mg/m) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 (1000000U) and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients' conditions along with the efficacy and safety were assessed every two cycles.
Between 11/2018 and 01/2020, sixty-four patients were enrolled. In the sixty-four evaluable patients, the disease control rate (DCR) and overall response rate (ORR) were 76.6% and 43.75%, respectively. The median follow-up time was 12.1 (range 7.1-22.4) months. The median PFS was 5.7 (range 1.63-15.8) months. The median OS was 14.2 (range 2.9-22.0) months. The most common adverse event was fever (75%). The incidence of III/IV grade neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival.
The AGIG chemo-immunotherapy regimen has presented favorable ORR, OS, and manageable toxicities as first-line therapeutic strategy of advanced pancreatic cancer treatment. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response.
https://clinicaltrials.gov/. identifier NCT03768687.
迄今为止，化疗仍然是不可切除胰腺腺癌的唯一有效治疗方法。在过去几年中，免疫抗癌治疗的关注度急剧上升。AGIG是一种新型的化疗免疫治疗方案，它将纳米白蛋白结合型紫杉醇+吉西他滨化疗与序贯重组白细胞介素-2（IL-2）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）治疗相结合。我们进行了一项单臂前瞻性II期研究，以确定AGIG方案一线治疗晚期胰腺癌的疗效和安全性。
所有患者在第1天和第8天静脉注射纳米白蛋白结合型紫杉醇（125mg/m²）和吉西他滨（1000mg/m²），每三周一次，化疗后第3 - 5天皮下注射白细胞介素-2（1000000U）和GM-CSF（100μg）。主要终点是根据实体瘤疗效评价标准1.1版确定的客观缓解率（ORR）。次要终点包括安全性、无进展生存期（PFS）、总生存期（OS）。每两个周期评估患者的病情以及疗效和安全性。
在2018年11月至2020年1月期间，纳入了64例患者。在64例可评估患者中，疾病控制率（DCR）和总缓解率（ORR）分别为76.6%和43.75%。中位随访时间为12.1（范围7.1 - 22.4）个月。中位PFS为5.7（范围1.63 - 15.8）个月。中位OS为14.2（范围2.9 - 22.0）个月。最常见的不良事件是发热（75%）。III/IV级中性粒细胞减少的发生率为4.69%。在亚组分析中，我们发现血液中嗜酸性粒细胞计数比基线水平升高三倍以上预示着生存期更长。
AGIG化疗免疫治疗方案作为晚期胰腺癌治疗的一线治疗策略，具有良好的ORR、OS和可管理的毒性。该方案可能是身体状况良好患者的一种新型可靠治疗选择。治疗效率的提高可能与非特异性免疫反应的激活有关。
