Robella Manuela, Vaira Marco, Argenziano Monica, Spagnolo Rita, Cavalli Roberta, Borsano Alice, Gentilli Sergio, De Simone Michele
Unit of Surgical Oncology, Candiolo Cancer Institute, IRCCS-FPO, Candiolo, Italy.
Department of Drug Science and Technology, University of Torino, Torino, Italy.
Front Pharmacol. 2019 Jun 25;10:669. doi: 10.3389/fphar.2019.00669. eCollection 2019.
Peritoneal carcinomatosis is a common metastatic pattern in ovarian, gastric, colorectal, and appendiceal cancer; systemic chemotherapy is the current standard of care for peritoneal metastatic disease; however, in a subset of patients its beneficial effect remains questionable. More effective perioperative chemotherapy is needed. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It's a safe and feasible approach that improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. Till now the drugs used in PIPAC for the treatment of the peritoneal carcinomatosis (PC) are cisplatin, doxorubicin, and oxaliplatin; as of yet, there are no data comparing different drug formulations and dosage schedules of PIPAC. Pegylated liposomal doxorubicin 1.5 mg/sm was aerosolized in PIPAC procedures. Pharmacokinetics analysis of 10 procedures performed with conventional doxorubicin solution at the dose of 1.5 mg/m were compared to 15 procedures with the same dose of pegylated liposomal doxorubicin (PLD). Significant differences between experimental groups were detected by one-way ANOVA followed by Bonferroni correction; a p value < 0.05 was considered statistically significant. A statistically different doxorubicin tissue concentration was observed for the doxorubicin solution compared to pegylated liposomal doxorubicin in the right parietal peritoneum and right diaphragm. In the Caelyx series a mean tissue concentration of 1.27 ± 1.33 mg/g was reported, while in the second one we registered a mean concentration of 3.1 ± 3.7 mg/g. The delivery of nano-particles in PIPAC was feasible, but pegylated liposomal concentrations are lower than standard doxorubicin formulation. Probably mechanical and physical properties of pressurized aerosol chemotherapy might alter their stability and cause structural disintegration.
腹膜癌病是卵巢癌、胃癌、结直肠癌和阑尾癌常见的转移模式；全身化疗是目前腹膜转移疾病的标准治疗方法；然而，在一部分患者中，其疗效仍存在疑问。需要更有效的围手术期化疗。加压腹腔内气溶胶化疗（PIPAC）是一种新的治疗方法，它在压力作用下将化疗药物以气溶胶的形式注入腹腔。与传统的腹腔内化疗相比，这是一种安全可行的方法，可提高化疗药物的局部生物利用度。到目前为止，PIPAC用于治疗腹膜癌病（PC）的药物有顺铂、阿霉素和奥沙利铂；截至目前，尚无比较PIPAC不同药物配方和给药方案的数据。在PIPAC手术中雾化了1.5mg/平方米的聚乙二醇化脂质体阿霉素。将15例使用相同剂量聚乙二醇化脂质体阿霉素（PLD）的手术与10例使用1.5mg/平方米常规阿霉素溶液的手术的药代动力学分析进行了比较。通过单因素方差分析并采用Bonferroni校正检测实验组之间的显著差异；p值<0.05被认为具有统计学意义。在右侧壁腹膜和右侧膈肌中，观察到阿霉素溶液与聚乙二醇化脂质体阿霉素的阿霉素组织浓度存在统计学差异。在Caelyx系列中，报告的平均组织浓度为1.27±1.33mg/g，而在第二个系列中，我们记录的平均浓度为3.1±3.7mg/g。纳米颗粒在PIPAC中的递送是可行的，但聚乙二醇化脂质体浓度低于标准阿霉素制剂。加压气溶胶化疗的机械和物理性质可能会改变其稳定性并导致结构解体。
