Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for gastric cancer with peritoneal metastases: A systematic review by the PIPAC UK collaborative

Gastric cancer is the fifth most common cause of cancer globally, affecting over a million patients each year (Sung et al., 2021). Despite recent advances in some other tumour types, gastric cancer continues to carry a poor prognosis, particularly in the metastatic setting where 1-year overall survival is approximately 20% (CRUK).

Peritoneal dissemination is common, with approximately 10–21% of patients presenting with synchronous peritoneal disease at diagnosis, though surgical cohort studies report up to 40% have occult peritoneal metastases at staging laparascopy (Thomassen et al., 2014, Rijken et al., 2021). In addition, it is the commonest site of disease recurrence following radical treatment (Yoo et al., 2000), and may be the only site of disease for up to 65% of patients (Koemans et al., 2021).

The presence of peritoneal disease is usually considered incurable even in the absence of other visceral metastases. Without treatment median overall survival (mOS) is only of 2.8 months (Koemans et al., 2021). Current standard of care for metastatic gastric cancer is systemic chemotherapy, with the addition of targeted therapy or immunotherapy for selected patients increasing mOS up to 16 months (Bang et al., 2010, Janjigian et al., 2021b). However, peritoneal disease poses additional complexities to the treating oncologist. Reduced blood supply and high interstitial pressure, resulting in poor penetration of drug into the peritoneum can lead to poor response to traditional systemic anti-cancer therapies (SACT). Peritoneal carcinomatosis can also result in distressing sequelae including pain, refractory ascites and bowel obstruction. This underlies the urgent need for novel treatment strategies in this setting.

Pressurised intraperitoneal aerosolized chemotherapy (PIPAC) was developed in 2011 as an innovative way to deliver chemotherapy directly into the peritoneum at high pressure (Solass et al., 2014). Early phase studies have confirmed the pharmacokinetic advantages of PIPAC; the pressure gradient created can overcome tumour interstitial pressure, resulting in higher concentration of chemotherapy in peritoneal tumour nodules and improved distribution throughout the peritoneal cavity, whilst minimising systemic absorption and potential toxicity. (Nadiradze et al., 2019).

Following its development in Germany, the procedure has been implemented across Europe via the establishment of stringent certification courses (Alyami et al., 2020). As such, the PIPAC technique is largely standardized across more than 60 centres (Sgarbura et al., 2021, Nowacki et al., 2018). However despite promise, it has not yet become routine practice worldwide, and for example, is not currently NICE approved for routine use in the UK (National Institute for Health and Care, 2020).

PIPAC is performed under general anesthesia during a laparoscopic procedure. Access to the abdomen is gained via 2 incisions (10–12 mm and 5 mm), through which 2 trocars are inserted. The abdomen is insufflated with CO2 to achieve normothermic capnoperitoneum (37◦c, 12 mmHg), after which the peritoneal cavity is explored, any ascitic fluid drained, peritoneal cancer index (PCI) score assessed and biopsies taken. A cytotoxic solution is nebulized and injected at high pressure using a procedure specific, patented device (CapnoPen®). For gastric cancer, cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 are the most commonly used agents (Nowacki et al., 2018). The therapeutic capnoperitoneum is maintained for 30 min, and then evacuated via a closed waste system. PIPAC can be repeated every 4–6 weeks, and can be given either alone (i.e. “unidirectional”) or in a “bidirectional” manner alongside systemic chemotherapy, when it is given in alternating cycles (for example 1–2 cycles of chemotherapy alternating with PIPAC).

Phase I and II data has been encouraging regarding the safety and tolerability of PIPAC for the management of peritoneal metastases from many primary tumour sites including ovarian, colorectal and gastric cancer. In addition, studies have confirmed feasibility of delivering multiple PIPAC treatments, and suggest improvement in survival, whilst maintaining patient quality of life (QOL). (Alyami et al., 2019).

The PIPAC UK Collaborative is a multi-disciplinary research group dedicated to establishing the role of PIPAC by developing future UK-based clinical trials to contribute to the international evidence base. This systematic review aims to evaluate the efficacy, tolerability and impact on QOL of PIPAC for the treatment of gastric cancer with peritoneal metastases (GCPM).

留言 (0)

沒有登入
gif