Mistry Priya, Mohamed Faheez, Dayal Sanjeev, Cecil Tom D, Moran Brendan J
Pharmacy Department, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK.
Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK.
Eur J Hosp Pharm. 2016 Jul;23(4):233-238. doi: 10.1136/ejhpharm-2016-000877. Epub 2016 Apr 5.
To explore the use of intraperitoneal chemotherapy in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy and highlight the challenges this provides for the hospital pharmacist.
A literature search for relevant articles was performed using MEDLINE, PubMed and Cochrane databases. The following keywords and phrases were used: 'hyperthermic intraperitoneal chemotherapy', 'early postoperative intraperitoneal chemotherapy', 'carrier solutions' and 'cytoreductive surgery'. Local experience was also shared, referencing national guidelines and published literature.
The rationale behind intraperitoneal chemotherapy is to directly administer drugs into the peritoneal cavity and achieve exposure of higher concentrations of cytotoxic agents to tumour nodules within the abdomen and on peritoneal surfaces for a prolonged period of time, without significant systemic toxicity. This has been widely demonstrated in intraoperative and early postoperative settings. Hydrophilic chemotherapy drugs with high molecular weights and permeable to the peritoneum, but slow plasma clearance create high concentrations of the drug in the peritoneal cavity, with lower systemic circulation. Commonly used drugs include , , , and . Newer drugs such as the taxanes and have also shown promise. Heat increases drug penetration into body tissues and destroys tumour cells directly by causing damage to cells that have inherently faulty heat regulation pathways and also increases the cytotoxic effect of selected chemotherapeutic agents. Optimal temperature for hyperthermic intraperitoneal drug administration is between 41 and 43°C in a carrier solution that is compatible with the drug chosen. For early postoperative intraperitoneal chemotherapy high molecular weight starch carrier solutions prolong intraperitoneal dwell time and exposure of drug to tumour cells. Drugs are administered intraoperatively with the abdomen open or closed for between 30 and 120 min depending on the drug chosen and local protocols. Drug doses are traditionally calculated using body surface area. Toxicity such as neutropenia is encountered far less than with systemic chemotherapy.
This paper discusses the rationale for intraperitoneal drug administration following cytoreductive surgery and describes appropriate drug selection, methods of drug delivery and potential challenges in the use of the intraperitoneal route. It provides evidence and practical guidance for hospital pharmacists who may be involved in the surgical management of peritoneal malignancy particularly in dose calculation, preparation and administration of intraperitoneal chemotherapy.
探讨腹腔内化疗联合肿瘤细胞减灭术治疗腹膜表面恶性肿瘤的应用，并强调这给医院药剂师带来的挑战。
使用MEDLINE、PubMed和Cochrane数据库对相关文章进行文献检索。使用了以下关键词和短语：“热灌注腹腔内化疗”“术后早期腹腔内化疗”“载体溶液”和“肿瘤细胞减灭术”。还分享了当地经验，参考了国家指南和已发表的文献。
腹腔内化疗的基本原理是将药物直接注入腹腔，使高浓度的细胞毒性药物长时间作用于腹部和腹膜表面的肿瘤结节，而无明显的全身毒性。这在术中及术后早期环境中已得到广泛证实。具有高分子量且可透过腹膜但血浆清除缓慢的亲水性化疗药物在腹腔内产生高浓度药物，而全身循环中的药物浓度较低。常用药物包括 、 、 、 和 。紫杉烷类等新药也显示出前景。热可增加药物向身体组织的渗透，并通过对热调节途径固有缺陷的细胞造成损伤直接破坏肿瘤细胞，还可增强某些化疗药物的细胞毒性作用。热灌注腹腔内给药的最佳温度在41至43°C之间，使用与所选药物相容的载体溶液。对于术后早期腹腔内化疗，高分子量淀粉载体溶液可延长腹腔内停留时间以及药物与肿瘤细胞的接触时间。根据所选药物和当地方案，在术中腹部开放或关闭的情况下给药30至120分钟。传统上药物剂量使用体表面积计算。与全身化疗相比，中性粒细胞减少等毒性反应的发生率要低得多。
本文讨论了肿瘤细胞减灭术后腹腔内给药的基本原理，描述了合适的药物选择、给药方法以及腹腔内途径使用中的潜在挑战。它为可能参与腹膜恶性肿瘤手术管理的医院药剂师提供了证据和实用指导，特别是在腹腔内化疗的剂量计算、配制和给药方面。
