Robella Manuela, De Simone Michele, Berchialla Paola, Argenziano Monica, Borsano Alice, Ansari Shoeb, Abollino Ornella, Ficiarà Eleonora, Cinquegrana Armando, Cavalli Roberta, Vaira Marco
Unit of Surgical Oncology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Department of Clinical and Biological Sciences, University of Torino, 10126 Torino, Italy.
Cancers (Basel). 2021 Mar 3;13(5):1060. doi: 10.3390/cancers13051060.
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative laparoscopic intraperitoneal chemotherapy approach with the advantage of a deeper tissue penetration. Thus far, oxaliplatin has been administered at an arbitrary dose of 92 mg/m, cisplatin at 7.5 mg/m and doxorubicin 1.5 mg/m. This is a model-based approach phase I dose escalation study with the aim of identifying the maximum tolerable dose of the three different drugs. The starting dose of oxaliplatin was 100 mg/m; cisplatin was used in association with doxorubicin: 15 mg/m and 3 mg/m were the respective starting doses. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE version 4.03). Thirteen patients were submitted to one PIPAC procedure. Seven patients were treated with cisplatin and doxorubicin and 6 patients with oxaliplatin; no dose limiting toxicities and major side effects were found. Common adverse events included postoperative abdominal pain and nausea. The maximum tolerable dose was not reached. The highest dose treated cohort (oxaliplatin 135 mg/m; cisplatin 30 mg/m and doxorubicin 6 mg/m) tolerated PIPAC well. Serological analyses revealed no trace of doxorubicin at any dose level. Serum levels of cis- and oxaliplatin reached a peak at 60-120 min after PIPAC and were still measurable in the circulation 24 h after the procedure. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m and 6 mg/m, respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m. The dosages achieved to date are the highest ever used in PIPAC.
加压腹腔内气溶胶化疗（PIPAC）是一种创新的腹腔镜腹腔内化疗方法，具有更深的组织穿透优势。迄今为止，奥沙利铂的给药剂量为任意的92mg/m²，顺铂为7.5mg/m²，阿霉素为1.5mg/m²。这是一项基于模型的I期剂量递增研究，旨在确定这三种不同药物的最大耐受剂量。奥沙利铂的起始剂量为100mg/m²；顺铂与阿霉素联合使用：起始剂量分别为15mg/m²和3mg/m²。根据不良事件通用术语标准（CTCAE版本4.03）评估安全性。13名患者接受了一次PIPAC手术。7名患者接受顺铂和阿霉素治疗，6名患者接受奥沙利铂治疗；未发现剂量限制性毒性和主要副作用。常见的不良事件包括术后腹痛和恶心。未达到最大耐受剂量。接受最高剂量治疗的队列（奥沙利铂135mg/m²；顺铂30mg/m²和阿霉素6mg/m²）对PIPAC耐受性良好。血清学分析在任何剂量水平均未发现阿霉素痕迹。顺铂和奥沙利铂的血清水平在PIPAC后60 - 120分钟达到峰值，术后24小时循环中仍可测量。顺铂和阿霉素分别以30mg/m²和6mg/m²的剂量作为PIPAC使用可能是安全的；奥沙利铂可腹腔内使用剂量为135mg/m²。迄今为止达到的剂量是PIPAC中使用过的最高剂量。
