一项评估胰腺腺癌切除术后行腹腔内热化疗的前瞻性、I/II 期、开放性、初步试验，以评估其安全性。
A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma.
机构信息
Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.
Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany.
出版信息
Ann Surg Oncol. 2021 Dec;28(13):9086-9095. doi: 10.1245/s10434-021-10187-8. Epub 2021 Jun 15.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a common fatal disease with unfavorable prognosis, even after oncological resection. To improve survival, adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested. Whether HIPEC entails disproportional short-term mortality is unknown and a prospectively determined adverse events profile is lacking. Since both pancreatic resection and HIPEC may relevantly influence morbidity and mortality, this uncontrolled single-arm, open-label, phase I/II pilot trial was designed to assess the 30-day mortality rate, treatment feasibility, and adverse events connected with HIPEC after oncological pancreatic surgery.
METHODS
This trial recruited patients scheduled for PDAC resection. A sample size of 16 patients receiving study interventions was estimated to establish a predefined margin of treatment-associated short-term mortality with a power of > 80%. Patients achieving complete macroscopic resection received HIPEC with gemcitabine administered at 1000 mg/m body surface area heated to 42 °C for 1 hour.
RESULTS
Within 30 days after intervention, no patient died or experienced any adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related adverse events were prospectively documented and categorized as expected or unexpected. This trial supports that the actual mortality rate after PDAC resection and HIPEC is below 10%. HIPEC treatment proved feasible in 89% of patients allocated to intervention. Pancreatic fistulas, as key complications after pancreas surgery, occurred in 3/13 patients under risk.
CONCLUSION
Combined pancreas resection and gemcitabine HIPEC proved feasible and safe, with acceptable morbidity and mortality. Based on these results, further clinical evaluation can be justified.
REGISTRATION NUMBER
NCT02863471 ( http://www.clinicaltrials.gov ).
背景
胰腺导管腺癌（PDAC）是一种常见的致命疾病，预后不良，即使进行了肿瘤切除也是如此。为了提高生存率，已经提出了添加腹腔热灌注化疗（HIPEC）的建议。HIPEC 是否会导致不成比例的短期死亡率尚不清楚，也缺乏前瞻性确定的不良事件概况。由于胰腺切除术和 HIPEC 都可能对发病率和死亡率产生重大影响，因此设计了这项非对照的单臂、开放标签、I/II 期试验，以评估接受肿瘤胰腺手术后 30 天死亡率、治疗可行性以及与 HIPEC 相关的不良事件。
方法
本试验招募了计划接受 PDAC 切除术的患者。估计需要 16 名接受研究干预的患者样本量，以建立与治疗相关的短期死亡率的预定界限，其置信度>80%。接受完全宏观切除的患者接受 HIPEC，吉西他滨以 1000mg/m 体表面积给药，加热至 42°C 持续 1 小时。
结果
在干预后 30 天内，没有患者死亡或经历任何与 HIPEC 相关的高于 3 级的不良事件。此外，前瞻性地记录了与治疗相关的不良事件，并分为预期或意外。本试验支持 PDAC 切除和 HIPEC 后实际死亡率低于 10%。在分配给干预的 89%的患者中，HIPEC 治疗被证明是可行的。在 3/13 例存在风险的胰腺手术后，发生了关键并发症胰腺瘘。
结论
联合胰腺切除术和吉西他滨 HIPEC 证明是可行且安全的，具有可接受的发病率和死亡率。基于这些结果，可以进行进一步的临床评估。
登记号
NCT02863471（http://www.clinicaltrials.gov）。
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