Feasibility, Safety, and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastasis: A Registry Study

Florian Kurtz, Florian Struller, Philipp Horvath, Wiebke Solass, Hans Bösmüller, Alfred Königsrainer, Marc A Reymond, Florian Kurtz, Florian Struller, Philipp Horvath, Wiebke Solass, Hans Bösmüller, Alfred Königsrainer, Marc A Reymond

Abstract

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system with superior pharmacological properties for treating peritoneal metastasis (PM). Safety and efficacy results of PIPAC with cisplatin/doxorubicin or oxaliplatin from a registry cohort are presented.

Methods: IRB-approved registry study. Retrospective analysis. No predefined inclusion criteria, individual therapeutic recommendation by the interdisciplinary tumor board. Safety assessment with CTCAE 4.0. Histological assessment of tumor response by an independent pathologist using the 4-tied peritoneal regression grading system (PRGS). Mean PRGS and ascites volume were assessed at each PIPAC.

Results: A total of 142 PIPAC procedures were scheduled in 71 consecutive patients with PM from gastric (n = 26), colorectal (n = 17), hepatobiliary/pancreatic (n = 9), ovarian (n = 6), appendiceal (n = 5) origin, pseudomyxoma peritonei (n = 4), and other tumors (n = 3). Mean age was 58 ± 13 years. Patients were heavily pretreated. Mean PCI was 19 ± 13. Laparoscopic nonaccess rate was 11/142 procedures (7.7%). Mean number of PIPAC/patient was 2. All patients were eligible for safety analysis. There was no procedure-related mortality. There were 2.8% intraoperative and 4.9% postoperative complications. 39 patients underwent more than one PIPAC and were eligible for efficacy analysis, and PRGS could be assessed in 36 of them. In 24 patients (67%), PRGS improved or remained unchanged at PIPAC#2, reflecting tumor regression or stable disease. Ascites was present in 24 patients and diminished significantly under therapy. Median survival was 11.8 months (95% CI: 7.45-16.2 months) from PIPAC#1.

Conclusion: PIPAC is feasible, safe, and well-tolerated and can induce histological regression in a significant proportion of pretreated PM patients. This trial is registered with NCT03210298.

Figures

Figure 1
Figure 1
Patient flowchart.
Figure 2
Figure 2
Ascites volume at PIPAC#1, PIPAC#2, and PIPAC#3. There is a significant decrease of ascites volume under therapy (ANOVA, p = 0.03).
Figure 3
Figure 3
Overall survival probability (Kaplan-Meyer) of pretreated patients with pseudomyxoma peritonei (PMP), malignant peritoneal mesothelioma (MESO), and peritoneal metastasis of colorectal (CRC), appendiceal (APP), ovarian (OV), hepatobiliary-pancreatic (HBP), and gastric (GC) origins. Survival calculated from the date of first PIPAC.

References

    1. Lambert L. A. Looking up: recent advances in understanding and treating peritoneal carcinomatosis. CA: A Cancer Journal for Clinicians. 2015;65(4):284–298. doi: 10.3322/caac.21277.
    1. Markman M. Intraperitoneal antineoplastic drug delivery: rationale and results. The Lancet Oncology. 2003;4(5):277–283. doi: 10.1016/S1470-2045(03)01074-X.
    1. Dedrick R. L., Flessner M. F. Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. Journal of the National Cancer Institute. 1997;89(7):480–487. doi: 10.1093/jnci/89.7.480.
    1. Flessner M. F. Pharmacokinetic problems in peritoneal drug administration: an update after 20 years. Pleura and Peritoneum. 2016;1(4):183–191. doi: 10.1515/pp-2016-0022.
    1. Markman M. Chemotherapy: limited use of the intraperitoneal route for ovarian cancer-why? Nature Reviews. Clinical Oncology. 2015;12(11):628–630. doi: 10.1038/nrclinonc.2015.177.
    1. Dakwar G. R., Shariati M., Willaert W., Ceelen W., De Smedt S. C., Remaut K. Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis - mission possible? Advanced Drug Delivery Reviews. 2017;108:13–24. doi: 10.1016/j.addr.2016.07.001.
    1. Reymond M. A., Hu B., Garcia A., et al. Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator. Surgical Endoscopy. 2000;14(1):51–55. doi: 10.1007/s004649900010.
    1. 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. Annals of Surgical Oncology. 2014;21(2):553–559. doi: 10.1245/s10434-013-3213-1.
    1. Solass W., Herbette A., Schwarz T., et al. Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. Surgical Endoscopy. 2012;26(3):847–852. doi: 10.1007/s00464-011-1964-y.
    1. Khosrawipour V., Khosrawipour T., Kern A. J. P., et al. Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a post-mortem swine model. Journal of Cancer Research and Clinical Oncology. 2016;142(11):2275–2280. doi: 10.1007/s00432-016-2234-0.
    1. Solaß W., Hetzel A., Nadiradze G., Sagynaliev E., Reymond M. A. Description of a novel approach for intraperitoneal drug delivery and the related device. Surgical Endoscopy. 2012;26(7):1849–1855. doi: 10.1007/s00464-012-2148-0.
    1. Eveno C., Haidara A., Ali I., Pimpie C., Mirshahi M., Pocard M. Experimental pharmacokinetics evaluation of chemotherapy delivery by PIPAC for colon cancer: first evidence for efficacy. Pleura and Peritoneum. 2017;2(2):103–110. doi: 10.1515/pp-2017-0015.
    1. Jacquet P., Stuart O. A., Chang D., Sugarbaker P. H. 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.
    1. 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. Annals of Surgery. 2006;244(1):106–112. doi: 10.1097/01.sla.0000218089.61635.5f.
    1. Tempfer C. B. Pressurized intraperitoneal aerosol chemotherapy as an innovative approach to treat peritoneal carcinomatosis. Medical Hypotheses. 2015;85(4):480–484. doi: 10.1016/j.mehy.2015.07.001.
    1. Blanco A., Giger-Pabst U., Solass W., Zieren J., Reymond M. A. Renal and hepatic toxicities after pressurized intraperitoneal aerosol chemotherapy (PIPAC) Annals of Surgical Oncology. 2013;20(7):2311–2316. doi: 10.1245/s10434-012-2840-2.
    1. Robella M., Vaira M., De Simone M. Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis. World Journal of Surgical Oncology. 2016;14(1):p. 128. doi: 10.1186/s12957-016-0892-7.
    1. Nadiradze G., Giger-Pabst U., Zieren J., Strumberg D., Solass W., Reymond M. A. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. Journal of Gastrointestinal Surgery. 2016;20(2):367–373. doi: 10.1007/s11605-015-2995-9.
    1. Khomyakov V., Ryabov A., Ivanov A., et al. Bidirectional chemotherapy in gastric cancer with peritoneal metastasis combining intravenous XELOX with intraperitoneal chemotherapy with low-dose cisplatin and doxorubicin administered as a pressurized aerosol: an open-label, Phase-2 study (PIPAC-GA2) Pleura and Peritoneum. 2016;1(3):159–166. doi: 10.1515/pp-2016-0017.
    1. Tempfer C. B., Celik I., Solass W., 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.
    1. Tempfer C. B., Winnekendonk G., Solass W., et al. Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: a phase 2 study. Gynecologic Oncology. 2015;137(2):223–228. doi: 10.1016/j.ygyno.2015.02.009.
    1. Demtröder C., Solass W., Zieren J., Strumberg D., Giger-Pabst U., Reymond M. A. Pressurized intraperitoneal aerosol chemotherapy with oxaliplatin in colorectal peritoneal metastasis. Colorectal Disease. 2016;18(4):364–371. doi: 10.1111/codi.13130.
    1. Graversen M., Detlefsen S., Bjerregaard J. K., Pfeiffer P., Mortensen M. B. Peritoneal metastasis from pancreatic cancer treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC) Clinical & Experimental Metastasis. 2017;34(5):309–314. doi: 10.1007/s10585-017-9849-7.
    1. Khosrawipour T., Khosrawipour V., Giger-Pabst U. Pressurized intra peritoneal aerosol chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma. PLoS One. 2017;12(10, article e0186709) doi: 10.1371/journal.pone.0186709.
    1. Falkenstein T. A., Götze T. O., Ouaissi M., Tempfer C. B., Giger-Pabst U., Demtröder C. First clinical data of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as salvage therapy for peritoneal metastatic biliary tract cancer. Anticancer Research. 2018;38(1):373–378. doi: 10.21873/anticanres.12232.
    1. Grass F., Vuagniaux A., Teixeira-Farinha H., Lehmann K., Demartines N., Hübner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. The British Journal of Surgery. 2017;104(6):669–678. doi: 10.1002/bjs.10521.
    1. , consulted on January 03, 2018.
    1. Lauer U. M., Schell M., Beil J., et al. Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis. Clinical Cancer Research. 2018;24(18):4388–4398. doi: 10.1158/1078-0432.CCR-18-0244.
    1. , consulted on January 03, 2018.
    1. He Z., Zhao T. T., Xu H. M., et al. Efficacy and safety of intraperitoneal chemotherapy in patients with advanced gastric cancer: a cumulative meta-analysis of randomized controlled trials. Oncotarget. 2017;8(46):81125–81136. doi: 10.18632/oncotarget.20818.
    1. Elit L., Oliver T. K., Covens A., et al. Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with metaanalyses. Cancer. 2007;109(4):692–702. doi: 10.1002/cncr.22466.
    1. Levine E. A., Votanopoulos K. I., Shen P., et al. A multicenter randomized trial to evaluate hematologic toxicities after hyperthermic intraperitoneal chemotherapy with oxaliplatin or mitomycin in patients with appendiceal tumors. Journal of the American College of Surgeons. 2018;226(4):434–443. doi: 10.1016/j.jamcollsurg.2017.12.027.
    1. van Driel W. J., Koole S. N., Sikorska K., et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. New England Journal of Medicine. 2018;378(3):230–240. doi: 10.1056/NEJMoa1708618.
    1. Provencher D. M., Gallagher C. J., Parulekar W. R., et al. OV21/PETROC: a randomized gynecologic cancer intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer. Annals of Oncology. 2018;29(2):431–438. doi: 10.1093/annonc/mdx754.
    1. Armstrong D. K., Bundy B., Wenzel L., et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. The New England Journal of Medicine. 2006;354(1):34–43. doi: 10.1056/NEJMoa052985.
    1. Walker J. L., Armstrong D. K., Huang H. Q., et al. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a gynecologic oncology group study. Gynecologic Oncology. 2006;100(1):27–32. doi: 10.1016/j.ygyno.2005.11.013.
    1. Bonvalot S., Cavalcanti A., le Péchoux C., et al. Randomized trial of cytoreduction followed by intraperitoneal chemotherapy versus cytoreduction alone in patients with peritoneal sarcomatosis. European Journal of Surgical Oncology. 2005;31(8):917–923. doi: 10.1016/j.ejso.2005.04.010.
    1. Solass W., Giger-Pabst U., Zieren J., Reymond M. A. 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.
    1. Solass W., Sempoux C., Detlefsen S., Carr N. J., Bibeau F. Peritoneal sampling and histological assessment of therapeutic response in peritoneal metastasis: proposal of the peritoneal regression grading score (PRGS) Pleura and Peritoneum. 2016;1(2):99–107. doi: 10.1515/pp-2016-0011.
    1. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.03: June 14, 2010) Bethesda, MD, USA: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute; 2009.
    1. Dindo D., Demartines N., Clavien P. A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of Surgery. 2004;240(2):205–213. doi: 10.1097/.
    1. Hübner M., Teixeira Farinha H., Grass F., et al. Feasibility and safety of pressurized intraperitoneal aerosol chemotherapy for peritoneal carcinomatosis: a retrospective cohort study. Gastroenterology Research and Practice. 2017;2017:7. doi: 10.1155/2017/6852749.6852749
    1. Nowacki M., Alyami M., Villeneuve L., et al. Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: an international survey study. European Journal of Surgical Oncology. 2018;44(7):991–996. doi: 10.1016/j.ejso.2018.02.014.
    1. Tempfer C., Giger-Pabst U., Hilal Z., Dogan A., Rezniczek G. A. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Archives of Gynecology and Obstetrics. 2018;298(2):243–257. doi: 10.1007/s00404-018-4784-7.
    1. Graversen M., Detlefsen S., Bjerregaard J. K., Fristrup C. W., Pfeiffer P., Mortensen M. B. Prospective, single-center implementation and response evaluation of pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal metastasis. Therapeutic Advances in Medical Oncology. 2018;10 doi: 10.1177/1758835918777036.
    1. Satoh Y., Ichikawa T., Motosugi U., et al. Diagnosis of peritoneal dissemination: comparison of 18F-FDG PET/CT, diffusion-weighted MRI, and contrast-enhanced MDCT. AJR. American Journal of Roentgenology. 2011;196(2):447–453. doi: 10.2214/AJR.10.4687.
    1. Ceelen W. P. Scoring histological regression in peritoneal carcinomatosis: does it count? Pleura and Peritoneum. 2016;1(2):65–66. doi: 10.1515/pp-2016-0012.
    1. Tempfer C. B., Rezniczek G. A., Ende P., Solass W., Reymond M. A. Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin in women with peritoneal carcinomatosis: a cohort study. Anticancer Research. 2015;35(12):6723–6729.
    1. Struller F., Horvath P., Solass W., Weinreich F. J., Konigsrainer A., Reymond M. A. Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis (PIPAC-GA1) Journal of Clinical Oncology. 2017;35(Supplement 4):p. 99. doi: 10.1200/JCO.2017.35.4_suppl.99.
    1. Teixeira Farinha H., Grass F., Kefleyesus A., et al. Impact of pressurized intraperitoneal aerosol chemotherapy on quality of life and symptoms in patients with peritoneal carcinomatosis: a retrospective cohort study. Gastroenterology Research and Practice. 2017;2017:10. doi: 10.1155/2017/4596176.4596176
    1. Odendahl K., Solass W., Demtröder C., et al. Quality of life of patients with end-stage peritoneal metastasis treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC) European Journal of Surgical Oncology. 2015;41(10):1379–1385. doi: 10.1016/j.ejso.2015.06.001.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다