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Open Access 01-02-2014 | Gastrointestinal Oncology

Intraperitoneal Chemotherapy of Peritoneal Carcinomatosis Using Pressurized Aerosol as an Alternative to Liquid Solution: First Evidence for Efficacy

Authors: Wiebke Solass, MD, Reinhold Kerb, MD, Thomas Mürdter, PhD, Urs Giger-Pabst, MD, Dirk Strumberg, MD, Clemens Tempfer, MD, MBA, Jürgen Zieren, MD, Matthias Schwab, MD, Marc André Reymond, MD, MBA

Published in: Annals of Surgical Oncology | Issue 2/2014

Abstract

Background

Peritoneal carcinomatosis (PC) is an unmet medical need. Despite recent improvements, systemic chemotherapy has limited efficacy. We report the first application of intraperitoneal chemotherapy as a pressurized aerosol in human patients.

Methods

Three end-stage patients with advanced PC from gastric, appendiceal, and ovarian origin were treated as a compassionate therapy. All patients had received previous systemic chemotherapy. A pressurized aerosol of CO₂ loaded with doxorubicin 1.5 mg/m² and cisplatin 7.5 mg/m² (pressurized intraperitoneal aerosol chemotherapy, PIPAC) was applied into the abdomen for 30 min at a pressure of 12 mmHg and a temperature of 37 °C.

Results

No side-effects >2 CTCAE were observed, and the procedures were well tolerated. Early hospital discharge was possible (days 2–5). Nuclear presence of doxorubicin was documented throughout the peritoneum, reaching high local concentration (≤4.1 μmol/g) and plasma concentration was low (4.0–6.2 ng/ml). PIPAC created no significant adhesions, could be repeated, and was applied 6×, 4×, and 2×. Two patients showed a complete and one a partial histological remission. Mean survival after the first PIPAC was 288 days. One patient is alive after 567 days.

Conclusions

PIPAC shows superior pharmacological properties with high local concentration and low systemic exposure. PIPAC can induce regression of PC in chemoresistant tumors, using 10 % of a usual systemic dose.

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Griffiths RW, Zee YK, Evans S, Mitchell CL, Kumaran GC, Welch RS, Jayson GC, Clamp AR, Hasan J. Outcomes after multiple lines of chemotherapy for platinum-resistant epithelial cancers of the ovary, peritoneum, and fallopian tube. Int J Gynecol Cancer. 2011;21(1):58-65.PubMedCrossRef

Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6(8):583-92. Review.PubMedCrossRef

Macrì A, Fortugno A, Saladino E. Rationale and techniques of CRS and peritoneal chemohyperthermia. World J Gastrointest Oncol. 2011;3(12):169-74.PubMedCentralPubMedCrossRef

Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13(8):e362-9.PubMedCrossRef

Dedrick RL, Flessner MF. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst. 1997;89:480-7.PubMedCrossRef

Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, Lorimier G, Dubè P, Glehen O. 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.PubMedCrossRef

Reymond MA, Hu B, Garcia A, et al. Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator. Surg Endosc. 2000;14:51-5.PubMedCrossRef

Heldin CH, Rubin K, Pietras K, Ostman A. High interstitial fluid pressure – an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806-13. Review.PubMedCrossRef

Solaß W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012;26(7):1849-55.PubMedCrossRef

10.

Solass W, Herbette A, Schwarz T, Hetzel A, Sun JS, Dutreix M, Reymond MA. Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination capnoperitoneum: proof of concept. Surg Endosc. 2012;26(3):847-52.PubMedCentralPubMedCrossRef

11.

Elias D, Souadka A, Fayard F, Mauguen A, Dumont F, Honore C, Goere D. Variation in the peritoneal cancer index scores between surgeons and according to when they are determined (before or after cytoreductive surgery). Eur J Surg Oncol. 2012;38(6):503-8.PubMedCrossRef

12.

Solaß W, Giger U, Borgstedt U, Zieren J, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol. 2013 Jun 14 [Epub ahead of print].

13.

http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm, Accessed 31 Dec 2012.

14.

Sugarbaker PH, Van der Speeten K, Anthony Stuart O, Chang D. Impact of surgical and clinical factors on the pharmacology of intraperitoneal doxorubicin in 145 patients with peritoneal carcinomatosis. Eur J Surg Oncol. 2011;37(8):719-26.PubMedCrossRef

15.

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.PubMedCrossRef

16.

Esquis P, Consolo D, Magnin G, Pointaire P, Moretto P, Ynsa MD, Beltramo JL, Drogoul C, Simonet M, Benoit L, Rat P, Chauffert B. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis. Ann Surg. 2006;244(1):106-12.PubMedCrossRef

17.

Ozols RF, Young RC, Speyer JL, Sugarbaker PH, Greene R, Jenkins J, Myers CE. Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res. 1982;42(10):4265-9.PubMed

18.

Markman M. Intraperitoneal antineoplastic drug delivery: rationale and results. Lancet Oncol. 2003;4:277-83.PubMedCrossRef

19.

Blanco A, Giger U, Solass W, Cruciger O, Zieren J, Reymond MA. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Ann Surg Oncol. 2013;20(7):2311-6. PubMedCentralPubMedCrossRef

Title: Intraperitoneal Chemotherapy of Peritoneal Carcinomatosis Using Pressurized Aerosol as an Alternative to Liquid Solution: First Evidence for Efficacy
Authors: Wiebke Solass, MD
Reinhold Kerb, MD
Thomas Mürdter, PhD
Urs Giger-Pabst, MD
Dirk Strumberg, MD
Clemens Tempfer, MD, MBA
Jürgen Zieren, MD
Matthias Schwab, MD
Marc André Reymond, MD, MBA
Publication date: 01-02-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue 2/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-013-3213-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Intraperitoneal Chemotherapy of Peritoneal Carcinomatosis Using Pressurized Aerosol as an Alternative to Liquid Solution: First Evidence for Efficacy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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