Sugarbaker Paul H, Stuart O Anthony
Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, DC, USA.
J Gastrointest Oncol. 2021 Apr;12(Suppl 1):S99-S109. doi: 10.21037/jgo-2020-02.
Worldwide, the surgical management of pancreas cancer using the Whipple procedure results in long-term survival in approximately 20% of patients when there is a R0 resection. Local recurrence within the resection site and peritoneal metastases are a prominent part of this treatment failure. Gemcitabine was used for a regional chemotherapy treatment strategy. Doses and schedules of chemotherapy routinely used for systemic treatment were administered as hyperthermic intraperitoneal chemotherapy (HIPEC) in the operating room. Then patients went on to receive 6 months of long-term normothermic intraperitoneal chemotherapy (NIPEC) with gemcitabine. Data was gathered to determine a pharmacologic rationale and safety of this monotherapy with gemcitabine. The use of intraperitoneal gemcitabine was well supported by pharmacologic data. The peritoneal surface exposure as measured by pharmacokinetic studies showed the area under the curve (AUC) of intraperitoneal concentration times time divided by plasma concentration times time to be 95-507. Regarding the safety of HIPEC gemcitabine in 12 patients, a single class III adverse event that resolved by radiologic intervention occurred. In patients with resected pancreas cancer treated with HIPEC gemcitabine the morbidity and mortality rate was not increased over historical data of resection alone. Also, six cycles of NIPEC gemcitabine were well tolerated in eight of eight eligible patients with seven patients completing 6 months of long-term intraperitoneal treatment. Local recurrence and peritoneal metastases were absent. Median survival was 29 months and five patients survived longer than 2 years. These early data suggest that intraperitoneal gemcitabine given under hyperthermic conditions in the operating theater and long-term through an intraperitoneal port is safe. Also, in this pilot study long-term local control with intraperitoneal gemcitabine occurred. Intraperitoneal gemcitabine may improve local-regional control of resected pancreas cancer. This may lead to more successful multimodality strategies.
在全球范围内，对于胰腺癌采用惠普尔手术进行外科治疗时，若实现R0切除，约20%的患者可获得长期生存。切除部位的局部复发和腹膜转移是这种治疗失败的主要原因。吉西他滨被用于区域化疗治疗策略。常规用于全身治疗的化疗剂量和方案在手术室中作为热灌注腹腔化疗（HIPEC）给药。然后患者继续接受为期6个月的吉西他滨常温腹腔化疗（NIPEC）。收集数据以确定这种吉西他滨单一疗法的药理学依据和安全性。腹腔内使用吉西他滨得到了药理学数据的有力支持。通过药代动力学研究测量的腹膜表面暴露显示，腹腔内浓度乘以时间除以血浆浓度乘以时间的曲线下面积（AUC）为95 - 507。关于12例患者中HIPEC吉西他滨的安全性，发生了1例通过放射学干预解决的III级不良事件。在接受HIPEC吉西他滨治疗的胰腺癌切除患者中，发病率和死亡率并未高于单纯切除的历史数据。此外，在8例符合条件的患者中，有8例对6个周期的NIPEC吉西他滨耐受性良好，其中7例患者完成了6个月的长期腹腔内治疗。未出现局部复发和腹膜转移。中位生存期为29个月，5例患者存活超过2年。这些早期数据表明，在手术室高温条件下给予腹腔内吉西他滨并通过腹腔内端口进行长期给药是安全的。此外，在这项初步研究中，腹腔内吉西他滨实现了长期局部控制。腹腔内吉西他滨可能会改善切除胰腺癌的局部区域控制。这可能会带来更成功的多模式治疗策略。
