The use of PIPAC (pressurized intraperitoneal aerosol chemotherapy) in gynecological oncology: a statement by the German “Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)”, the Swiss and Austrian AGO, and the North-Eastern German Society of Gynaecologic Oncology
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Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288–294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234–1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615–619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105–112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324–1330, 2009).
PIPAC is a highly experimental method for treating patients with ovarian, tubal, and peritoneal cancer. To date, only three studies have investigated a total of 184 patients with peritoneal carcinomatosis (Grass, Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669–678, 2017). Only some of those studies were phase I/II studies that included PIPAC for patients with different indications and different cancer entities. It is important to keep in mind that the PIPAC approach is associated with relatively high toxicity. To date, no systematic dose-finding studies have been reported. Moreover, no studies have reported improvements in progression-free or overall survival associated with PIPAC therapy.
Randomized phase III studies are required to evaluate the effect of this therapy compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should not be performed outside the framework of prospective, controlled studies.
KeywordsPIPAC Ovarian cancer Peritoneal cancer Tubal cancer Therapy Chemotherapy
AMD: manuscript writing. DF: manuscript editing. PH: manuscript editing, project development. VH: manuscript editing. CM: manuscript editing. MM: manuscript editing. AR manuscript editing. KT: manuscript editing. PW: manuscript editing, project development. JS: manuscript writing, project development
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
This study was not funded.
Human and animal participants
This article does not contain any studies with human participants or animals performed by any of the authors.
- 2.Foley OW, Rauh-Hain JA, del Carmen MG (2013) Recurrent epithelial ovarian cancer: an update on treatment. Oncology (Williston Park) 27(288–94):98Google Scholar
- 3.du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J (2009) Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer 115:1234–1244CrossRefPubMedGoogle Scholar
- 8.Ledermann JA, Harter P, Gourley C et al (2016) Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 17:1579–1589CrossRefPubMedGoogle Scholar
- 11.Wenzel L et al (2016) Patient-reported outcomes of a phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube, and primary peritoneal carcinoma. NCI-supplied agent: bevacizumab. NCT011o67712, a GOG/NRG trial. SGO 2016; Abstract 7Google Scholar
- 12.Walker JL et al (2016) A phase III clinical trial of bevacizumab with IV versus IP chemotherapy in ovarian, fallopian tube, and primary peritoneal carcinoma. NCI-supplied agent: bevacizumab. NCT01167712, a GOG/NRG trial (GOG 252). SGO 2016; Abstract 6 2016Google Scholar
- 19.Solass WKR, Mürdter T, Giger-Pabst U, Strumberg D, Tempfer C, Zieren J, Schwab M, Reymond MA (2014) Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 21:553–559CrossRefPubMedGoogle Scholar
- 38.Reymond MA, Solass W (2014) Pressurized intraperitoneal aerosol chemotherapy (PIPAC)—cancer under pressure. De Gruyter, BerlinGoogle Scholar
- 39.http://www.awmf.org/uploads/tx_szleitlinien/032-035-OLl_Ovarialkarzinom_2016-10.pdf. Accessed 28 Sept 2017
- 40.Mobus V, Wandt H, Frickhofen N et al (2007) Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol 25:4187–4193CrossRefPubMedGoogle Scholar
- 47.Herman TS, Teicher BA, Cathcart KN, Kaufmann ME, Lee JB, Lee MH (1988) Effect of hyperthermia on cis-diamminedichloroplatinum(II) (rhodamine 123)2[tetrachloroplatinum(II)] in a human squamous cell carcinoma line and a cis-diamminedichloroplatinum(II)-resistant subline. Cancer Res 48:5101–5105PubMedGoogle Scholar
- 54.Girshally R, Demtroder C, Albayrak N, Zieren J, Tempfer C, Reymond MA (2016) Pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 14:253CrossRefPubMedPubMedCentralGoogle Scholar
- 59.Trimbos JB, Parmar M, Vergote I et al (2003) International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 95:105–112CrossRefPubMedGoogle Scholar
- 60.Harter P, Hahmann M, Lueck HJ et al (2009) Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I Trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol 16:1324–1330CrossRefPubMedGoogle Scholar