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Published in: World Journal of Surgical Oncology 1/2016

Open Access 01-12-2016 | Research

Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis

Authors: Manuela Robella, Marco Vaira, Michele De Simone

Published in: World Journal of Surgical Oncology | Issue 1/2016

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Abstract

Background

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented.

Methods

Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin + doxorubicin every 6 weeks at 37 °C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2.

Results

Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy.

Conclusions

These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.
Literature
1.
go back to reference Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28(1):63–8.CrossRefPubMed Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28(1):63–8.CrossRefPubMed
2.
go back to reference Hanker LC, Loibl S, Burchardi N, AGO and GINECO study group, et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol. 2012;23(10):2605–12.CrossRefPubMed Hanker LC, Loibl S, Burchardi N, AGO and GINECO study group, et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol. 2012;23(10):2605–12.CrossRefPubMed
3.
go back to reference Rivera F, Vega-Villegas ME, López-Brea MF. Chemotherapy of advanced gastric cancer. Cancer Treat Rev. 2007;33(4):315–24.CrossRefPubMed Rivera F, Vega-Villegas ME, López-Brea MF. Chemotherapy of advanced gastric cancer. Cancer Treat Rev. 2007;33(4):315–24.CrossRefPubMed
4.
go back to reference Chua TC, Yan TD, Morris DL. Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management. Can J Surg. 2009;52(1):59–64.PubMedPubMedCentral Chua TC, Yan TD, Morris DL. Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management. Can J Surg. 2009;52(1):59–64.PubMedPubMedCentral
5.
go back to reference Sugarbaker PH. Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology. Cancer Treat Res. 1996;82:79–100.CrossRefPubMed Sugarbaker PH. Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology. Cancer Treat Res. 1996;82:79–100.CrossRefPubMed
6.
go back to reference Ung L, Chua TC, Morris DL. Cure for peritoneal metastases? An evidence-based review. ANZ J Surg. 2013;83(11):821–6.CrossRefPubMed Ung L, Chua TC, Morris DL. Cure for peritoneal metastases? An evidence-based review. ANZ J Surg. 2013;83(11):821–6.CrossRefPubMed
7.
go back to reference Gill RS, Al-Adra DP, Nagendran J, et al. Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity. J Surg Oncol. 2011;104(6):692–8.CrossRefPubMed Gill RS, Al-Adra DP, Nagendran J, et al. Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity. J Surg Oncol. 2011;104(6):692–8.CrossRefPubMed
8.
go back to reference Solass W, Kerb R, Mürdter T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol. 2014;21(2):553–9.CrossRefPubMedPubMedCentral Solass W, Kerb R, Mürdter T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol. 2014;21(2):553–9.CrossRefPubMedPubMedCentral
9.
go back to reference Tempfer CB, Solass W, Reymond MA. Pressurized intraperitoneal chemotherapy (PIPAC) in women with gynecologic malignancies: a review. Wien Med Wochenschr. 2014;164(23–24):519–28.CrossRefPubMed Tempfer CB, Solass W, Reymond MA. Pressurized intraperitoneal chemotherapy (PIPAC) in women with gynecologic malignancies: a review. Wien Med Wochenschr. 2014;164(23–24):519–28.CrossRefPubMed
10.
go back to reference Tempfer CB, Winnekendonk G, Solass W, et al. Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: a phase 2 study. Gynecol Oncol. 2015;137(2):223–8.CrossRefPubMed Tempfer CB, Winnekendonk G, Solass W, et al. Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: a phase 2 study. Gynecol Oncol. 2015;137(2):223–8.CrossRefPubMed
11.
go back to reference Nadiradze G, Giger-Pabst U, Zieren J, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. J Gastrointest Surg. 2015;28 [Epub ahead of print]. Nadiradze G, Giger-Pabst U, Zieren J, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. J Gastrointest Surg. 2015;28 [Epub ahead of print].
12.
go back to reference Demtröder C, Solass W, Zieren J, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2015;24 [Epub ahead of print]. Demtröder C, Solass W, Zieren J, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin in colorectal peritoneal metastasis. Colorectal Dis. 2015;24 [Epub ahead of print].
13.
go back to reference Oyais A, Solass W, Zieren J, Reymond MA, Giger-Pabst U et al. Occupational health aspects of pressurised intraperitoneal aerosol chemotherapy (PIPAC): confirmation of harmlessness. Zentralbl Chir. 2014 [Epub ahead of print]. Oyais A, Solass W, Zieren J, Reymond MA, Giger-Pabst U et al. Occupational health aspects of pressurised intraperitoneal aerosol chemotherapy (PIPAC): confirmation of harmlessness. Zentralbl Chir. 2014 [Epub ahead of print].
14.
go back to reference Solass W, Giger-Pabst U, Zieren J, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol. 2013;20(11):3504–11.CrossRefPubMedPubMedCentral Solass W, Giger-Pabst U, Zieren J, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol. 2013;20(11):3504–11.CrossRefPubMedPubMedCentral
15.
go back to reference Blanco A, Giger-Pabst U, Solass W, Zieren J, Reymond MA. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 2013;20(7):2311–6.CrossRefPubMedPubMedCentral Blanco A, Giger-Pabst U, Solass W, Zieren J, Reymond MA. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 2013;20(7):2311–6.CrossRefPubMedPubMedCentral
16.
go back to reference Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefPubMed Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefPubMed
17.
go back to reference Esquis P, Consolo D, Magnin G, et al. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann Surg. 2006;244(1):106–12.CrossRefPubMedPubMedCentral Esquis P, Consolo D, Magnin G, et al. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann Surg. 2006;244(1):106–12.CrossRefPubMedPubMedCentral
18.
go back to reference Jacquet P, Stuart OA, Chang D, Sugarbaker PH. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs. 1996;7(5):596–603.CrossRefPubMed Jacquet P, Stuart OA, Chang D, Sugarbaker PH. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs. 1996;7(5):596–603.CrossRefPubMed
19.
go back to reference Battelli C, Campo M, Buss MK, Awtrey CS, Konstantinopoulos PA. Safety and outcome of patients treated with a modified outpatient intraperitoneal regimen for epithelial ovarian, primary peritoneal or fallopian tube cancer. Chemotherapy. 2013;59(4):251–9.CrossRefPubMed Battelli C, Campo M, Buss MK, Awtrey CS, Konstantinopoulos PA. Safety and outcome of patients treated with a modified outpatient intraperitoneal regimen for epithelial ovarian, primary peritoneal or fallopian tube cancer. Chemotherapy. 2013;59(4):251–9.CrossRefPubMed
20.
go back to reference Fujiwara K, Markman M, Morgan M, Coleman RL. Intraperitoneal carboplatin-based chemotherapy for epithelial ovarian cancer. Gynecol Oncol. 2005;97(1):10–5.CrossRefPubMed Fujiwara K, Markman M, Morgan M, Coleman RL. Intraperitoneal carboplatin-based chemotherapy for epithelial ovarian cancer. Gynecol Oncol. 2005;97(1):10–5.CrossRefPubMed
21.
go back to reference Verwaal F, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.CrossRefPubMed Verwaal F, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.CrossRefPubMed
22.
go back to reference Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22(16):3284–92.CrossRefPubMed Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22(16):3284–92.CrossRefPubMed
23.
go back to reference Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15(9):2426–32.CrossRefPubMed Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15(9):2426–32.CrossRefPubMed
24.
go back to reference Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681–5.CrossRefPubMed Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681–5.CrossRefPubMed
25.
go back to reference Armstrong DK, Bundy B, Wenzel L, Gynecologic Oncology Group, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34–43.CrossRefPubMed Armstrong DK, Bundy B, Wenzel L, Gynecologic Oncology Group, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34–43.CrossRefPubMed
26.
go back to reference Gadducci A, Conte PF. Intraperitoneal chemotherapy in the management of patients with advanced epithelial ovarian cancer: a critical review of the literature. Int J Gynecol Cancer. 2008;18(5):943–53.CrossRefPubMed Gadducci A, Conte PF. Intraperitoneal chemotherapy in the management of patients with advanced epithelial ovarian cancer: a critical review of the literature. Int J Gynecol Cancer. 2008;18(5):943–53.CrossRefPubMed
27.
go back to reference Trimble EL, Christian MC. Intraperitoneal chemotherapy for women with advanced epithelial ovarian carcinoma. Gynecol Oncol. 2006;100(1):3–4.CrossRefPubMed Trimble EL, Christian MC. Intraperitoneal chemotherapy for women with advanced epithelial ovarian carcinoma. Gynecol Oncol. 2006;100(1):3–4.CrossRefPubMed
28.
go back to reference Helm CW, Richard SD, Pan J, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry. Int J Gynecol Cancer. 2010;20(1):61–9.CrossRefPubMed Helm CW, Richard SD, Pan J, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry. Int J Gynecol Cancer. 2010;20(1):61–9.CrossRefPubMed
29.
go back to reference De Bree E, Helm CW. Hyperthermic intraperitoneal chemotherapy in ovarian cancer: rationale and clinical data. Expert Rev Anticancer Ther. 2012;12(7):895–911.CrossRefPubMed De Bree E, Helm CW. Hyperthermic intraperitoneal chemotherapy in ovarian cancer: rationale and clinical data. Expert Rev Anticancer Ther. 2012;12(7):895–911.CrossRefPubMed
30.
go back to reference Deraco M, Kusamura S, Virzì S, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial. Gynecol Oncol. 2011;122(2):215–20.CrossRefPubMed Deraco M, Kusamura S, Virzì S, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial. Gynecol Oncol. 2011;122(2):215–20.CrossRefPubMed
31.
go back to reference Ströhlein MA, Bulian DR, Heiss MM. Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer. Expert Rev Anticancer Ther. 2011;11(10):1505–8.CrossRefPubMed Ströhlein MA, Bulian DR, Heiss MM. Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer. Expert Rev Anticancer Ther. 2011;11(10):1505–8.CrossRefPubMed
32.
go back to reference Baratti D, Kusamura S, Cabras AD, et al. Lymph node metastases in diffuse malignant peritoneal mesothelioma. Ann Surg Oncol. 2010;17(1):45–53.CrossRefPubMed Baratti D, Kusamura S, Cabras AD, et al. Lymph node metastases in diffuse malignant peritoneal mesothelioma. Ann Surg Oncol. 2010;17(1):45–53.CrossRefPubMed
33.
go back to reference Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.CrossRefPubMed Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.CrossRefPubMed
34.
go back to reference Deraco M, Casali P, Inglese MG, et al. Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion. J Surg Oncol. 2003;83(3):147–53.CrossRefPubMed Deraco M, Casali P, Inglese MG, et al. Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion. J Surg Oncol. 2003;83(3):147–53.CrossRefPubMed
Metadata
Title
Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis
Authors
Manuela Robella
Marco Vaira
Michele De Simone
Publication date
01-12-2016
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2016
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-016-0892-7

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