INTRAPERITONEAL AEROSOL CHEMOTHERAPY UNDER PRESSURE (IACUP) – AN INNOVATIVE METHOD OF TREATMENT OF PATIENTS WITH PERITONEAL CARCINOMATOSIS

Widespread peritoneal carcinomatosis in gastric cancer, in fact, is the end-stage of the disease. The survival median of patients is no more than 3–6 months. Development of various methods of intraperitoneal chemotherapy can improve the prognosis of this category of patients.

Objective. To evaluate the efficacy and safety of intraperitoneal aerosol chemotherapy under pressure (IACUP) in patients with gastric cancer with peritoneal carcinomatosis.

Materials and methods. The treatment Protocol consisted of a laparotomy or laparoscopy for the staging of the tumor process, 3–4 courses of systemic chemotherapy scheme XELOX followed by conducting at least 3 sessions of intraperitoneal aerosol chemotherapy under pressure (IACUP) with an interval of 6 weeks on the background of chemotherapy. In the case of progression the patient was excluded from the study. Currently, the study included 27 patients with disseminated gastric cancer who underwent 46 procedures of IACUP. There were 8 men and 19 women. The average age of patients was 50.6 years.

Results. In the framework of the safety assessment of IACUP there were 3 cases of adverse effects. Two patients (7,4%) noted nausea for the first 2 days after running the session of IACUP. In one patient the iatrogenic perforation of the diaphragm during biopsy of the peritoneum with the development of carbonetworks occurred. The survival median was 11 months. One-year survival rate (by KaplanMeier) was 50.7%. 14 patients are alive and continue to participate in the study during the first year of observation.

Conclusion. Intraperitoneal aerosol chemotherapy under pressure (IACUP) is a simple, minimally invasive and safe method for the palliative treatment of patients with disseminated carcinomatosis of gastric cancer. We developed the treatment Protocol that allows us to achieve one-year survival of more than half of patients.

1. Berretta M., Fisichella R., Borsatti E., Lleshi A., Ioffredo S., Meneguzzo N., et al. Feasibility of intraperitoneal Trastuzumab treatment in a patient with peritoneal carcinomatosis from gastric cancer. Eur Rev Med Pharmacol Sci. 2014; 18 (5): 689–692.

2. Jemal A., Bray F., Center M. M., Ferlay J., Ward E., Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61 (2): 69–90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.

3. Sarela A., Miner T., Karpeh M., Coit D., Jaques D., Brennan M. Clinical outcomes with laparoscopic stage M1, unresected gastric adenocarcinoma. Ann Surg. 2006; 243 (2): 189–195.

4. Brenner H., Rothenbacher D., Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009; 472: 467–477. doi: 10.1007/978–1-60327–492–0_23.

5. Cappellani A., Zanghi A., Di Vita M., Zanet E., Veroux P., Cacopardo B., et al. Clinical and biological markers in gastric cancer: update and perspectives. Front Biosci (Schol Ed) 2010; 2: 403–412.

6. Kaprin A., Sobolev D., Khomyakov V. et al. Experience with hyperthermic intraoperative intraperitoneal chemotherapy in the treatment of locally advanced gastric cancer (Cyt+). Onkologiya Zhurnal imeni PA Gerzena. 2015; (1):67–70. 2015; (1):67–70. doi: 10.17116/onkolog20154167–70 (Russian).

7. Johanna В., Harry H. Y., Panos F. Systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer. Feb 2016. Available at: http://www.uptodate.com/ contents/systemic-therapy-for-locally-advanced-unresectable-and-metastatic-esophageal-and-gastric-cancer (Accessed: 02.03.2016)

8. Verwaal V., van Ruth S., de Bree E., van Sloothen G., van Tinteren H., Boot H., 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 Oct 15; 21 (20): 3737–3743.

9. Jacquet P., Stuart O., Chang D., Sugarbaker P. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anti-Cancer Drugs. 1996; 7 (5): 596–603. doi:10.1097/00001813– 199607000–00016.

10. Esquis P., Consolo D., Magnin G., Pointaire P., Moretto P., Ynsa M.D., et al. High Intra-abdominal Pressure Enhances the Penetration and Antitumor Effect of Intraperitoneal Cisplatin on Experimental Peritoneal Carcinomatosis. Annals of Surgery. 2006; 244 (1): 106–112. doi:10.1097/01. sla.0000218089.61635.5f.

11. Tempfer C., Celik I., Solass W., Buerkle B., Pabst U.G., Zieren J., et al. Activity of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: Preliminary clinical experience. Gynecologic Oncology. 2014; 132 (2): 307–311. doi:10.1016/j.ygyno.2013.11.022.

12. Wiebke S., Reinhold K., Thomas M., Urs Giger-Pabst, Dirk S., Clemens 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): 553–559.

13. Solass W., Kerb R., Mürdter T., Buerkle B., Pabst U.G., Zieren J., et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Annals of Surgical Oncology. 2013; 21 (2): 553–559. doi:10.1245/s10434–013–3213–1.

14. Jacquet P., Sugarbaker P. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996; 82: 359–374.

15. Elias D., Souadka A., Fayard F., Mauguen A., Dumont F., Honore C., et al. 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): 503–508.

16. Thomassen I., van Gestel Y., van Ramshorst B., Luyer M., Bosscha K., Nienhuijs S., et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014; 134 (3): 622–628.

17. Abbasi S., Taani H., Saad A., Badheeb A., Addasi A. Advanced gastric cancer in jordan from 2004 to 2008: a study of epidemiology and outcomes. Gastrointest Cancer Res. 2011; 4 (4): 122–127.

18. Griffiths R., Zee Y., Evans S., Mitchell C., Kumaran G., Welch R., et al. 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.

19. Macrì A., Fortugno A., Saladino E. Rationale and techniques of cytoreductive surgery and peritoneal chemohyperthermia. World J Gastrointest Oncol. 2011; 3 (12): 169–174.

20. Sugarbaker P., Ryan D. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012 Aug; 13 (8): e362–369.

21. Dedrick R., Flessner M. Pharmacokinetic Problems in Peritoneal Drug Administration: Tissue Penetration and Surface Exposure. JNCI Journal of the National Cancer Institute. 1997; 89 (7): 480–487. doi:10.1093/jnci/89.7.480.

22. Jacquet P., Stuart O., Chang D., Sugarbaker P. Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration. Anticancer Drugs. 1996; 7 (5): 596–603.

23. Solaß W., Hetzel A., Nadiradze G., Sagynaliev E., Reymond M. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc. 2012; 26 (7): 1849–1855. doi: 10.1007/s00464–012–2148–0. Epub 2012 May 12.

24. Solaß W., Giger-Pabst U., Zieren J., Reymond M. Pressurized intraperitoneal aerosol chemotherapy (pipac): occupational health and safety aspects. Annals of Surgical Oncology. 2013; 20 (11): 3504–3511. doi:10.1245/s10434–013–3039 x.