唑来膦酸作为可切除性胰腺导管腺癌患者新辅助围手术期治疗的研究
A Study of Zoledronic Acid as Neo-Adjuvant, Perioperative Therapy in Patients with Resectable Pancreatic Ductal Adenocarcinoma.
作者信息
Sanford Dominic E, Porembka Matthew R, Panni Roheena Z, Mitchem Jonathan B, Belt Brian A, Plambeck-Suess Stacey M, Lin Goldie, Denardo David G, Fields Ryan C, Hawkins William G, Strasberg Steven M, Lockhart A Craig, Wang-Gillam Andrea, Goedegebuure Simon Peter, Linehan David C
机构信息
Department of Surgery, Washington University - School of Medicine.
出版信息
J Cancer Ther. 2013 May;4(3):797-803. doi: 10.4236/jct.2013.43096.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by abundant granulocytic myeloid-derived suppressor cells (G-MDSC = CD45/Lin/CD33/CD11b/CD15), which infiltrate tumors and suppress anti-tumor immunity. We have previously demonstrated in a murine model of PDAC that zoledronic acid (ZA) depletes G-MDSC resulting in decreased tumor growth and improved survival. We report here the results of a phase 1 clinical trial (NCT00892242) using ZA as neo-adjuvant, perioperative therapy in patients with non-metastatic, resectable pancreatic adenocarcinoma.
METHODS
Eligible PDAC patients received ZA (4mg) IV 2 weeks prior to surgery. Patients then received 2 additional doses of ZA 4 weeks apart. Blood and bone marrow were obtained from patients prior to treatment with ZA and 3 months after surgery for analysis of G-MDSC by flow cytometry.
RESULTS
Twenty-three patients received pre-operative ZA with at least 6 months of follow-up Only 15 PDAC patients had non-metastatic PDAC, which was amenable to resection. ZA was well tolerated, and all adverse events were grade 1 or 2. The most common adverse events were fatigue, abdominal pain/discomfort, anorexia, and arthralgia. Of resected PDAC patients treated with ZA, 1- and 2-year overall survival (OS) was 85.7% and 33.3%, respectively, with a median OS of 18 months. This group had a 1- and 2-year progression-free survival (PFS) of 26.9% and 8.9%, respectively, with a median PFS of 12 months. The prevalence of G-MDSC was unchanged in the blood and bone marrow of PDAC patients pre- and post-treatment with ZA.
CONCLUSION
ZA is safe and well tolerated as neo-adjuvant, peri-operative therapy in PDAC patients. In this small study, we did not observe a difference in OS or PFS compared to historical controls. Also, there was no difference in the prevalence of G-MDSC in the blood and bone marrow of PDAC patients pre- and post-treatment with ZA.
背景
胰腺导管腺癌（PDAC）是一种侵袭性恶性肿瘤，其特征是有大量粒细胞性髓源性抑制细胞（G-MDSC = CD45/Lin/CD33/CD11b/CD15）浸润肿瘤并抑制抗肿瘤免疫。我们之前在PDAC小鼠模型中证明，唑来膦酸（ZA）可减少G-MDSC，从而导致肿瘤生长减缓并提高生存率。我们在此报告一项1期临床试验（NCT00892242）的结果，该试验使用ZA作为非转移性、可切除胰腺腺癌患者的新辅助围手术期治疗。
方法
符合条件的PDAC患者在手术前2周静脉注射ZA（4mg）。然后患者每隔4周再接受2剂ZA。在患者接受ZA治疗前及术后3个月采集血液和骨髓，通过流式细胞术分析G-MDSC。
结果
23例患者接受了术前ZA治疗，随访至少6个月。只有15例PDAC患者为非转移性PDAC，适合进行切除。ZA耐受性良好，所有不良事件均为1级或2级。最常见的不良事件是疲劳﹑腹痛/不适﹑厌食和关节痛。接受ZA治疗的切除PDAC患者中，1年和2年总生存率（OS）分别为85.7%和33.3%，中位OS为18个月。该组1年和2年无进展生存率（PFS）分别为26.9%和8.9%，中位PFS为12个月。PDAC患者在接受ZA治疗前后，血液和骨髓中G-MDSC的患病率没有变化。
结论
ZA作为PDAC患者的新辅助围手术期治疗是安全且耐受性良好的。在这项小型研究中，与历史对照相比，我们未观察到OS或PFS有差异。此外，PDAC患者在接受ZA治疗前后，血液和骨髓中G-MDSC的患病率也没有差异。
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