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http://dx.doi.org/10.5230/jgc.2020.20.e15

Recent Advances in Intra-peritoneal Chemotherapy for Gastric Cancer  

Chia, Daryl K.A. (Department of Surgery, University Surgical Cluster, National University Health System)
So, Jimmy Bok Yan (Department of Surgery, University Surgical Cluster, National University Health System)
Publication Information
Journal of Gastric Cancer / v.20, no.2, 2020 , pp. 115-126 More about this Journal
Abstract
Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.
Keywords
Gastric cancer; Peritoneal metastasis; Intraperitoneal chemotherapy; HIPEC; PIPAC;
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1 Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, et al. Randomized Phase III study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol 2013;43:972-980.   DOI
2 Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg 2017;104:669-678.   DOI
3 Nadiradze G, Giger-Pabst U, Zieren J, Strumberg D, Solass W, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis. J Gastrointest Surg 2016;20:367-373.   DOI
4 Khomyakov V, Ryabov A, Ivanov A, Bolotina L, Utkina A, Volchenko N, 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 Peritoneum 2016;1:159-166.   DOI
5 Alyami M, Bonnot PE, Villeneuve L, Bakrin N, Glehen O. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for nonresectable peritoneal carcinomatosis from gastric cancer. J Clin Oncol 2018;36:149.
6 Struller F, Horvath P, Solass W, Weinreich FJ, Strumberg D, Kokkalis MK, et al. Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis: a phase II study. Ther Adv Med Oncol 2019;11:1758835919846402.
7 Garg PK, Jara M, Alberto M, Rau B. The role of pressurized intraperitoneal aerosol chemotherapy in the management of gastric cancer: a systematic review. Pleura Peritoneum 2019;4:20180127.
8 Tavernier C, Passot G, Vassal O, Allaouchiche B, Decullier E, Bakrin N, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study. Surg Endosc 2019. [Epub ahead of print].
9 Alyami M, Hubner M, Grass F, Bakrin N, Villeneuve L, Laplace N, et al. Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications. Lancet Oncol 2019;20:e368-e377.   DOI
10 Khosrawipour V, Khosrawipour T, Kern AJ, Osma A, Kabakci B, Diaz-Carballo D, et al. Distribution pattern and penetration depth of doxorubicin after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in a postmortem swine model. J Cancer Res Clin Oncol 2016;142:2275-2280.   DOI
11 Hubner M, Teixeira Farinha H, Grass F, Wolfer A, Mathevet P, Hahnloser D, et al. Feasibility and safety of pressurized intraperitoneal aerosol chemotherapy for peritoneal carcinomatosis: a retrospective cohort study. Gastroenterol Res Pract 2017;2017:6852749.
12 Gockel I, Jansen-Winkeln B, Haase L, Rhode P, Mehdorn M, Niebisch S, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in gastric cancer patients with peritoneal metastasis (PM): results of a single-center experience and register study. J Gastric Cancer 2018;18:379-391.   DOI
13 Yu W. A review of adjuvant therapy for resected primary gastric cancer with an update on Taegu's phase III trial with intraperitoneal chemotherapy. Eur J Surg Oncol 2006;32:655-660.   DOI
14 Chu DZ, Lang NP, Thompson C, Osteen PK, Westbrook KC. Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer 1989;63:364-367.   DOI
15 Jacquet P, Sugarbaker PH. Peritoneal-plasma barrier. Cancer Treat Res 1996;82:53-63.   DOI
16 Yonemura Y, Canbay E, Li Y, Coccolini F, Glehen O, Sugarbaker PH, et al. A comprehensive treatment for peritoneal metastases from gastric cancer with curative intent. Eur J Surg Oncol 2016;42:1123-1131.   DOI
17 Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 2000;88:358-363.   DOI
18 Dedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 1978;62:1-11.
19 Oh SY, Kwon HC, Lee S, Lee DM, Yoo HS, Kim SH, et al. A Phase II study of oxaliplatin with low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) for gastric cancer patients with malignant ascites. Jpn J Clin Oncol 2007;37:930-935.   DOI
20 Yamao T, Shimada Y, Shirao K, Ohtsu A, Ikeda N, Hyodo I, et al. Phase II study of sequential methotrexate and 5-fluorouracil chemotherapy against peritoneally disseminated gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial. Jpn J Clin Oncol 2004;34:316-322.   DOI
21 Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol 2011;18:1575-1581.   DOI
22 Desiderio J, Chao J, Melstrom L, Warner S, Tozzi F, Fong Y, et al. The 30-year experience-a meta-analysis of randomised and high-quality non-randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer. Eur J Cancer 2017;79:1-14.   DOI
23 Witkamp AJ, de Bree E, Van Goethem R, Zoetmulder FA. Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy. Cancer Treat Rev 2001;27:365-374.   DOI
24 Hall JJ, Loggie BW, Shen P, Beamer S, Douglas Case L, McQuellon R, et al. Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for advanced gastric cancer. J Gastrointest Surg 2004;8:454-463.   DOI
25 Newhook TE, Agnes A, Blum M, Estrella JS, Das P, Ho L, et al. Laparoscopic hyperthermic intraperitoneal chemotherapy is safe for patients with peritoneal metastases from gastric cancer and may lead to gastrectomy. Ann Surg Oncol 2019;26:1394-1400.   DOI
26 Yarema RR, Ohorchak MA, Zubarev GP, Mylyan YP, Oliynyk YY, Zubarev MG, et al. Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: results of a single-centre retrospective study. Int J Hyperthermia 2014;30:159-165.   DOI
27 Yarema R, Mielko J, Fetsych T, Ohorchak M, Skorzewska M, Rawicz-Pruszynski K, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: a retrospective cooperative Central-Eastern European study. Cancer Med 2019;8:2877-2885.   DOI
28 Levine EA, Stewart JH 4th, Russell GB, Geisinger KR, Loggie BL, Shen P. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal surface malignancy: experience with 501 procedures. J Am Coll Surg 2007;204:943-953.   DOI
29 Sugarbaker PH, Alderman R, Edwards G, Marquardt CE, Gushchin V, Esquivel J, et al. Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy. Ann Surg Oncol 2006;13:635-644.   DOI
30 Yonemura Y, Ishibashi H, Hirano M, Mizumoto A, Takeshita K, Noguchi K, et al. Effects of neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy and neoadjuvant intraperitoneal/systemic chemotherapy on peritoneal metastases from gastric cancer. Ann Surg Oncol 2017;24:478-485.   DOI
31 Thomas F, Ferron G, Gesson-Paute A, Hristova M, Lochon I, Chatelut E. Increased tissue diffusion of oxaliplatin during laparoscopically assisted versus open heated intraoperative intraperitoneal chemotherapy (HIPEC). Ann Surg Oncol 2008;15:3623-3624.   DOI
32 Feingold PL, Kwong ML, Davis JL, Rudloff U. Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk for peritoneal carcinomatosis: a systematic review. J Surg Oncol 2017;115:192-201.   DOI
33 Pasqual EM, Bertozzi S, Londero AP, Brandolin D, Mariuzzi L, De Pellegrin A, et al. Microscopic peritoneal carcinomatosis in gastric cancer: prevalence, prognosis and predictive factors. Oncol Lett 2018;15:710-716.
34 Ikeguchi M, Kondou A, Oka A, Tsujitani S, Maeta M, Kaibara N. Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion. Eur J Surg 1995;161:581-586.
35 Sun J, Song Y, Wang Z, Gao P, Chen X, Xu Y, et al. Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials. BMC Cancer 2012;12:526.   DOI
36 Glehen O, Passot G, Villeneuve L, Vaudoyer D, Bin-Dorel S, Boschetti G, et al. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study. BMC Cancer 2014;14:183.   DOI
37 Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer 2017;20:111-121.   DOI
38 Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006;354:34-43.   DOI
39 Kamei T, Kitayama J, Yamaguchi H, Soma D, Emoto S, Konno T, et al. Spatial distribution of intraperitoneally administrated paclitaxel nanoparticles solubilized with poly (2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) in peritoneal metastatic nodules. Cancer Sci 2011;102:200-205.   DOI
40 Emoto S, Ishigami H, Hidemura A, Yamaguchi H, Yamashita H, Kitayama J, et al. Complications and management of an implanted intraperitoneal access port system for intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Jpn J Clin Oncol 2012;42:1013-1019.   DOI
41 Kono K, Yong WP, Okayama H, Shabbir A, Momma T, Ohki S, et al. Intraperitoneal chemotherapy for gastric cancer with peritoneal disease: experience from Singapore and Japan. Gastric Cancer 2017;20:122-127.   DOI
42 Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, et al. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol 2010;21:67-70.   DOI
43 Fujiwara Y, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, et al. Intraperitoneal docetaxel combined with S-1 for advanced gastric cancer with peritoneal dissemination. J Surg Oncol 2012;105:38-42.   DOI
44 Imano M, Peng YF, Itoh T, Nishikawa M, Satou T, Yasuda A, et al. A preliminary study of single intraperitoneal administration of paclitaxel followed by sequential systemic chemotherapy with S-1 plus paclitaxel for advanced gastric cancer with peritoneal metastasis. Anticancer Res 2012;32:4071-4075.
45 Li Z, Xue K, Ying X, Ji J. PHOENIX-GC trial: underpowered for significant results? J Clin Oncol 2019;37:167.
46 Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T. A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macroscopic peritoneal metastasis. Cancer 2013;119:3354-3358.   DOI
47 Fushida S, Kinoshita J, Kaji M, Hirono Y, Goda F, Yagi Y, et al. Phase I/II study of intraperitoneal docetaxel plus S-1 for the gastric cancer patients with peritoneal carcinomatosis. Cancer Chemother Pharmacol 2013;71:1265-1272.   DOI
48 Sugarbaker PH, Van der Speeten K. Surgical technology and pharmacology of hyperthermic perioperative chemotherapy. J Gastrointest Oncol 2016;7:29-44.
49 Chan DY, Syn NL, Yap R, Phua JN, Soh TI, Chee CE, et al. Conversion surgery post-intraperitoneal paclitaxel and systemic chemotherapy for gastric cancer carcinomatosis peritonei. Are we ready? J Gastrointest Surg 2017;21:425-433.   DOI
50 Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, et al. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol 2018;36:1922-1929.   DOI
51 Ishigami H, Yamaguchi H, Yamashita H, Asakage M, Kitayama J. Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings. Gastric Cancer 2017;20:128-134.   DOI
52 Yu W, Whang I, Chung HY, Averbach A, Sugarbaker PH. Indications for early postoperative intraperitoneal chemotherapy of advanced gastric cancer: results of a prospective randomized trial. World J Surg 2001;25:985-990.   DOI
53 Aizawa M, Ishigami H, Yabusaki H, Nashimoto A, Imamoto H, Imano M, et al. Phase II study of intraperitoneal paclitaxel plus S-1/paclitaxel for gastric cancer with positive peritoneal cytology: CY-PHOENIX trial. J Clin Oncol 2017;35:96.
54 Hultman B, Lind P, Glimelius B, Sundbom M, Nygren P, Haglund U, et al. Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy. Acta Oncol 2013;52:824-830.   DOI
55 Cheong JH, Shen JY, Song CS, Hyung WJ, Shen JG, Choi SH, et al. Early postoperative intraperitoneal chemotherapy following cytoreductive surgery in patients with very advanced gastric cancer. Ann Surg Oncol 2007;14:61-68.   DOI
56 Solass W, Kerb R, Murdter T, Giger-Pabst U, Strumberg D, Tempfer C, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 2014;21:553-559.   DOI
57 Takahashi N, Kanda M, Yoshikawa T, Takiguchi N, Fujitani K, Miyamoto K, et al. A randomized phase II multicenter trial to explore efficacy of weekly intraperitoneal in comparison with intravenous paclitaxel administered immediately after gastrectomy to the patients with high risk of peritoneal recurrence: final results of the INPACT trial. Gastric Cancer 2018;21:1014-1023.   DOI