Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treatment of advanced ovarian cancer. A review of the literature

Objective: The majority of advanced ovarian cancer (OC) patients do not fully respond to systemic chemotherapy, thus complete cytoreduction can not be achieved in such cases. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been suggested as an alternative approach for these women. Our study aimed to review the literature regarding the application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in OC patients with peritoneal carcinomatosis (PC). Data source: Articles in the English language were searched in PubMed. Search terms included “PIPAC” and “ovarian cancer”. Methods of study selection: The authors evaluated all studies presenting an application of pressurised intraperitoneal aerosol chemotherapy (PIPAC) on ovarian cancer patients. The published guidelines for Systematic Reviews and Meta-analyses (PRISMA) were followed in the present systematic review which was performed based on the authors’ predetermined inclusion criteria. Tabulation: Table 1 presents the main characteristics and outcomes of the OC patients undergoing PIPAC. Integration: Study selection and data extraction were independently undertaken by two reviewers. Results: 235 patients from 15 studies retrieved from PubMed were included. Conclusions: Our results indicate that PIPAC is efficient and safe in selected OC patients with PC not responding to systemic chemotherapy. The toxicity is manageable and the quality of life sustained. Further, randomised controlled trials are warranted to confirm our findings.

Pressurized intraperitoneal aerosol chemotherapy; PIPAC; Ovarian cancer; Peritoneal metastasis

[1] Nadiradze G, Horvath P, Sautkin Y, Archid R, Weinreich FJ, Königsrainer A, et al. Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Cancers. 2019; 12: 34.

[2] Tempfer C, Giger-Pabst U, Hilal Z, Dogan A, Rezniczek GA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Archives of Gynecology and Obstetrics. 2018; 298: 243–257.

[3] Alyami M, Hübner M, Grass F, Bakrin N, Villeneuve L, Laplace N, et al. Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications. The Lancet Oncology. 2019; 20: e368–e377.

[4] Giger-Pabst U, Solass W, Buerkle B, Reymond M, Tempfer CB. Low-dose pressurized intraperitoneal aerosol chemotherapy (PI-PAC) as an alternative therapy for ovarian cancer in an octogenarian patient. Anticancer Research. 2015; 35: 2309–2314.

[5] Ceribelli C, Debs T, Chevallier A, Piche MA, Bereder JM. Initial experience of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a French hyperthermic intraperitoneal chemotherapy (HIPEC) expert center. Surgical Endoscopy. 2020; 34: 2803–2806.

[6] Tempfer CB, Winnekendonk G, Solass W, Horvat R, Giger-Pabst U, Zieren J, et al. Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: A phase 2 study. Gynecologic Oncology. 2015; 137: 223–228.

[7] Alyami M, Mercier F, Siebert M, Bonnot P, Laplace N, Vil-leneuve L, et al. Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. European Journal of Surgical Oncology. 2021; 47: 128–133.

[8] Sgarbura O, Hübner M, Alyami M, Eveno C, Gagnière J, Pache B, et al. Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: a multicenter study. European Journal of Surgical Oncology. 2019; 45: 2386–2391.

[9] Siebert M, Alyami M, Mercier F, Gallice C, Villeneuve L, Laplace N, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in association with systemic chemotherapy and bevacizumab, evaluation of safety and feasibility. A single center comparative study. European Journal of Surgical Oncology. 2021; 47: 139–142.

[10] Kurtz F, Struller F, Horvath P, Solass W, Bösmüller H, Königsrainer A, et al. Feasibility, Safety, and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastasis: A Registry Study. Gastroenterology Research and Practice. 2018; 2018: 2743985.

[11] Tempfer CB, Hilal Z, Dogan A, Petersen M, Rezniczek GA. Concentrations of cisplatin and doxorubicin in ascites and peritoneal tumor nodules before and after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasis. European Journal of Surgical Oncology. 2018; 44: 1112–1117.

[12] Tempfer CB, Giger-Pabst U, Seebacher V, Petersen M, Dogan A, Rezniczek GA. A phase I, singlearm, open-label, dose escalation study of intraperitoneal cisplatin and doxorubicin in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Gynecologic Oncology. 2018; 150: 23–30.

[13] Tempfer CB, Hartmann F, Hilal Z, Rezniczek GA. Intraperitoneal cisplatin and doxorubicin as maintenance chemotherapy for unresectable ovarian cancer: a case report. BMC Cancer. 2017; 17: 26.

[14] Tempfer CB, Rezniczek GA, Ende P, Solass W, Reymond M. Pressurized Intraperitoneal Aerosol Chemotherapy with Cisplatin and Doxorubicin in Women with Peritoneal Carcinomatosis: A Cohort Study. Anticancer Research. 2015; 35: 6723–6729.

[15] Solass W, Kerb R, Mürdter T, Giger-Pabst U, Strumberg D, Tempfer C, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Annals of Surgical Oncology. 2014; 21: 553–559.

[16] De Simone M, Vaira M, Argenziano M, Berchialla P, Pisacane A, Cinquegrana A, et al. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with Oxaliplatin, Cisplatin, and Doxorubicin in Patients with Peritoneal Carcinomatosis: An Open-Label, Single-Arm, Phase II Clinical Trial. Biomedicines. 2020; 8: 102.

[17] Hoskovec D, Krška Z, Vočka M, Dytrych P. PIPAC - overview of the method and first use in the Czech Republic. Rozhledy v Chirurgii. 2020; 99: 529–533.