Skip to main content

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal metastases of pancreas and biliary tract cancer

Clinical & Experimental Metastasis volume 35, pages 635–640 (2018)Cite this article

Abstract

Data on the effectivness of PIPAC in patients with peritoneal metastases of pancreaticobiliary origin is scarce. We here present further proof of treatment efficacy in this subset of patients. Repetitive PIPAC treatment with low-dose cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 body surface area every 6 weeks and prospective data collection. Documentation included microscopic histological regression, median overall survival and treatment-related adverse events. Twelve patients with a median age of 57 years (range 43–78 years) were included. Six patients suffered from pertioneal metastases of pancreatic adenocarcinoma (PDAC) and six patients from cholangiocarcinoma (CC). In total 23 cycles of PIPAC were adminstered with the median number of PIPAC cycles being two (range 1–4). Complete tumor regression was found in four patients and major regression in one patient. Median overall survival after the first PIPAC cycle was 12.7 months for PDAC patients and 15.1 months for CC patients. 11 of the 12 patients are still alive after a median follow-up of 438 days. There were no CTCAE Grade 3 or 4 complications. PIPAC is an innovative and attractive treatment option in the salvage situation for patients with peritoneal metastases of pancreaticobiliary tumors after failure of systemic chemotherapy. In 40% of the patients histological regression can be induced. Further studies are warranted to further elucidate treatment efficacy.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Klempnauer J, Ridder GJ, Bektas H, Pichlmayr R (1995) Surgery for exocrine pancreatic cancer—who are the 5- and 10-year survivors? Oncology 52(5):353–359

    CAS  Article  Google Scholar 

  2. Beger HG, Rau B, Gansauge F, Leder G, Schwarz M, Poch B (2008) Pancreatic cancer—low survival rates. Dtsch Arztebl Int 105(14):255–262

    PubMed  PubMed Central  Google Scholar 

  3. Heeckt P, Safi F, Binder T, Büchler M (1992) Free intraperitoneal tumors cells in pancreatic cancer—significance for clinical course and therapy. Chirurg 63(7):563–567

    CAS  PubMed  Google Scholar 

  4. Sudo K, Ishihara T, Hirata N et al (2014) Randomized controlled study of gemcitabine plsu S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer. Cancer Chemother Pharmacol 73:389–396

    CAS  Article  Google Scholar 

  5. Tabarnero J, Chiorean EG, Infante JR et al (2015) Prognostic factors of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. Oncologist 20:143–150

    Article  Google Scholar 

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

    Article  Google Scholar 

  7. Odendahl K, Solass W, Demtröder C, Giger-Pabst U et al (2015) Quality of life of patients with end-stage peritoneal metastasis treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Eur J Surg Oncol 41:1379–1385

    CAS  Article  Google Scholar 

  8. Teixeira Frainha H, Grass F, Kefleyesus A, Achtari C et al (2017) Impact of pressurized intraperitoneal aerosol chemotherapy on quality of life and symptoms in patients with peritoneal carcinomatosis: a retrospective cohort analysis. Gastroenterol Res Pract 2017:4596176

    Google Scholar 

  9. Graversen M, Detlefsen S, Bjerregaard JK, Pfeiffer P et al (2017) Peritoneal metastasis from pancreatic cancer treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Clin Exp Metastasis 34(5):309–314

    CAS  Article  Google Scholar 

  10. Falkenstein TA, Götze TO, Ouaissi M, Tempfer CB, Giger-Pabst U, Demtröder C (2018) First clinical data of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as salvage therapy for peritoneal metastatic biliary tract cancer. Anticancer Res 38:373–378

    PubMed  Google Scholar 

  11. Sleeman JP (2017) PIPAC puts pressure on peritoneal metastases from pancreatic cancer. Clin Exp Metastasis 34(5):291–293

    CAS  Article  Google Scholar 

  12. Kurtz F, Struller F, Horvath P, Solass W, Bösmüller H, Königsrainer A, Reymond MA. Feasibility, safety and efficacy of Pressurizes IntraPeritoneal Aerosol Chemotherapy (PIPAC) for peritoneal metastases: a registry study. Gastroenterol Res Pract. https://doi.org/10.1155/2017/6852749

    Article  Google Scholar 

  13. Solass W, Kerb R, MuÈrdter T, Giger-Pabst U et al (2014) Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 21:553–559

    Article  Google Scholar 

  14. Demtröder C, Solass W, Zieren J, Strumberg D et al (2016) Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis 18:364–371

    Article  Google Scholar 

  15. Nadiradze G, Giger-Pabst U, Zieren J, Strumberg D et al (2016) Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. J Gastrointest Surg 20:367–373

    Article  Google Scholar 

  16. Sugarbaker PH (2015) Management of peritoneal metastases—basic concepts. J BUON 20(Suppl. 1):S2–S11

    PubMed  Google Scholar 

  17. GoÈhler D, Khosrawipour V, Khosrawipour T, Diaz-Carballo D et al (2017) Technical description of the microinjection pump (MIP) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC). Surg Endosc 31:1778–1784

    Article  Google Scholar 

  18. Khosrawipour V, Khosrawipour T, Falkenstein TA, Diaz-Carballo D et al (2016) Evaluating the effect of micropump position, internal pressure and doxorubicin dosage on efficacy of pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in an ex vivo model. Anticancer Res 36:4595–4600

    CAS  Article  Google Scholar 

  19. Solass W, Giger-Pabst U, Zieren J, Reymond MA (2013) Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol 20:3504–3511

    Article  Google Scholar 

  20. Solass W, Sempoux C, Detlefsen S, Carr NJ et al (2016) Peritoneal sampling and histological assessment of therapeutiv response in peritoneal metastasis: proposal of the peritoneal regression grading score (PRGS). Pleura Peritoneum 1:99–108

    Google Scholar 

  21. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Published: May 28, 2009 (v4.03: June 14, 2010). U.S. Department of Health and Human Services. National Institutes of Health, National Cancer Institute

  22. Sugarbaker PH, Stuart A, Bijelic L (2011) Intrapertioneal gemcitabine chemotherapy treatment for patients with resected pancreatic cancer: rationale and report of early data. Int J Surg Oncol 2011:161862

    PubMed  PubMed Central  Google Scholar 

  23. Tentes AA, Kyziridis D, Kakolyris S, Pallas N et al (2012) Preliminary results of hyperthermic intraperitoneal chemotherapy as an adjuvant in resectable pancreatic cancer. Gastroenterol Res Pract 2012:506571

    Article  Google Scholar 

  24. Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M et al (2013) Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 31:23–29

    CAS  Article  Google Scholar 

  25. Franko J, Shi Q, Meyers JP, Maughan TS et al (2016) Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomized trials from the Analysis and Research in Cancer of Digestive System (ARCAD) database. Lancet Oncol 12:1709–1719

    Article  Google Scholar 

  26. Ceelen WP, Flessner MF (2010) Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence. Nat Rev Clin Oncol 7:108–115

    Article  Google Scholar 

  27. Jang SH, Wientjes MG, Au JLS (2001) Enhancement of paclitaxel delivery to solid tumors by apoptosis-inducing pretreatment: effect of treatment schedule. JPharmacolExp Ther 296:1035–1042

    CAS  Google Scholar 

  28. Esquis P, Consolo D, Magnin G, Pointaire P et al (2006) High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann Surg 244:106–112

    Article  Google Scholar 

  29. Khosrawipour T, Khosrawipour V, Giger-Pabst U (2017) Pressurized intra peritoneal aerosol chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma. PLoS ONE 12:e0186709

    Article  Google Scholar 

  30. Tempfer CB, Winnekendonk G, Solass W, Horvat R et al (2015) Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer. A phase 2 study. Gynecol Oncol 137:223–228

    CAS  Article  Google Scholar 

  31. Struller F, Horvath P, Solass W et al (2017) Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis (PIPAC-GA1). ASCO GI meeting 2017; abstract 99

Download references

Author information

Affiliations

  1. Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany

    Philipp Horvath, Stefan Beckert, Florian Struller, Alfred Königsrainer & Marc André Reymond

  2. National Center for Pleura and Peritoneum, Comprehensive Cancer Center South-Western Germany, Tübingen, Germany

    Marc André Reymond

Authors
  1. Philipp Horvath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefan Beckert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Florian Struller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alfred Königsrainer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marc André Reymond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philipp Horvath.

Ethics declarations

Disclosures

Marc Andre Reymond holds several patents for PIPAC and related technologies and shareholder of Capnomed GmbH, Villigendorf, Germay.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Horvath, P., Beckert, S., Struller, F. et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal metastases of pancreas and biliary tract cancer. Clin Exp Metastasis 35, 635–640 (2018). https://doi.org/10.1007/s10585-018-9925-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-018-9925-7

Keywords

  • PIPAC
  • Peritoneal metastases
  • Pancreas
  • Cholangiocellular
  • Regression