Elsevier

The Lancet Oncology

Volume 20, Issue 7, July 2019, Pages e368-e377
The Lancet Oncology

Review
Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications

https://doi.org/10.1016/S1470-2045(19)30318-3Get rights and content

Summary

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12–15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62–88% was reported for patients with ovarian cancer (median survival of 11–14 months), 50–91% for gastric cancer (median survival of 8–15 months), 71–86% for colorectal cancer (median survival of 16 months), and 67–75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.

Introduction

Peritoneal metastasis is a heterogeneous group of primary disease or metastatic spread within the abdominal cavity. The most frequent conditions concern patients with ovarian (up to 46% at initial presentation), gastric (14%), and colorectal (5%) primary tumours, and patients with peritoneal mesothelioma.1, 2, 3, 4 A common feature of peritoneal metastasis is a reduced response to systemic chemotherapy and poor prognosis compared with other metastatic sites, at least in the recurrent setting.5, 6, 7

Intraperitoneal chemotherapy has been proposed as an alternative approach for these patients to improve tissue concentrations and to reduce systemic toxicity.8, 9, 10 This approach is a valid option in several types of malignancies in the adjuvant setting, such as ovarian and gastric cancer, for which phase 3 trials have been done.8, 11, 12 Long-term survival has been reported for different disease entities when combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).13, 14, 15, 16, 17 However, high morbidity and mortality and the unclear role of HIPEC have led to reduced acceptance of this technique within the medical community, despite growing but still controversial high-level evidence.18, 19, 20

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) has been proposed as an alternative mode for intraperitoneal drug delivery in certain situations, claiming improved distribution, enhanced tissue uptake, better tolerance, and repeatability using minimally invasive access.21, 22 The intriguing concept and favourable initial reports23, 24 have triggered the adoption of PIPAC as a drug delivery technique, mainly within Europe (appendix p 1).

We did a systematic review with the aim of detailing the rationale and technique of PIPAC and critically assessing the available evidence of its feasibility, safety, and tolerance and its use in potential indications other than ovarian and gastric cancer.

Section snippets

Literature search strategy and selection criteria

Medical subject heading (MeSH) terms “intraperitoneal” AND “chemotherapy” AND “pressurised” were used to search MEDLINE, Embase, the Cochrane Database of Systematic Review, and the Cochrane Central Register of Controlled Trials without language restrictions. Pertinent references and electronic links were hand-searched, and cross-referencing was done for selected articles. The search was limited to studies published between Jan 1, 2011 (the year PIPAC was first used in humans) and Jan 31, 2019.

Findings

Our systematic literature review identified 106 publications on PIPAC, with a substantial increase in the number of articles published since 2016 (appendix p 2). Excluding 25 preclinical studies, 24 reviews or narrative reports, 10 trial proposals, 2 unpublished conference reports, only 45 clinical studies, including case studies and occupational health studies, were identified (figure 1). Considering overlapping patient cohorts, our analysis included 1810 PIPAC procedures in 838 patients. The

Discussion

PIPAC is a new treatment alternative for patients with peritoneal metastasis and has undergone initial evaluation. Based on 1810 procedures in 838 patients, PIPAC can be considered a feasible, safe, and well tolerated treatment with no negative effect on quality of life. Oncological efficacy has been documented, according to different assessment tools, in 50–88% of patients with advanced peritoneal metastasis who are refractory to standard treatment. The prospective PIPAC registry (NCT03210298)

Conclusion

In summary, PIPAC can be considered a safe and promising treatment alternative for patients with advanced isolated refractory peritoneal disease. Other indications are being studied according to the IDEAL framework, such as prophylactic, neoadjuvant, or adjuvant treatment strategies including treatment combinations with systemic regimens. Reliable results should be available within the next 5–10 years.

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