Long-term survival after hyperthermic intraperitoneal chemotherapy using mitomycin C or oxaliplatin in colorectal cancer patients with synchronous peritoneal metastases: A nationwide comparative study

Published:April 18, 2020DOI:



      In the Netherlands, limited variability exists in performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among centers treating colorectal peritoneal metastases (PM), except for the intraperitoneal drug administration. This offers a unique opportunity to investigate any disparities in survival between the two most frequently used HIPEC regimens worldwide: mitomycin C (MMC) and oxaliplatin.


      This was a comparative, population-based cohort study of all Dutch patients diagnosed with synchronous colorectal PM who underwent CRS-HIPEC between 2014 and 2017. They were retrieved from the Netherlands Cancer Registry. Main outcome was overall survival (OS). The effect of the intraperitoneal drug on OS was investigated using multivariable Cox regression analysis.


      In total, 297 patients treated between 2014 and 2017 were included. Among them, 177 (59.6%) received MMC and 120 (40.4%) received oxaliplatin. Only primary tumor location was different between the two groups: more left-sided colon in the Oxaliplatin group (47.5% vs. 33.3%, respectively, p=0.048). The 1-, 2- and 3-year OS were 84.6% vs. 85.8%, 61.6% vs. 63.9% and 44.7% vs. 53.5% in patients treated with MMC and oxaliplatin, respectively. Median OS was 30.7 months in the MMC group vs. 46.6 months in the oxaliplatin group (p=0.181). In multivariable analysis, no influence of intraperitoneal drug on survival was observed (adjusted HR 0.77 [0.53–1.13]).


      Long-term survival between patients treated with either MMC or oxaliplatin during CRS-HIPEC was not significantly different.


      To read this article in full you will need to make a payment


        • Klaver Y.L.B.
        • Lemmens V.E.P.P.
        • Nienhuijs S.W.
        • Luyer M.D.P.
        • de Hingh Ihjt
        Peritoneal carcinomatosis of colorectal origin: incidence, prognosis and treatment options.
        World J Gastroenterol. 2012; 18: 5489-5494
        • Jayne D.G.
        • Fook S.
        • Loi C.
        • Seow-Choen F.
        Peritoneal carcinomatosis from colorectal cancer.
        Br J Surg. 2002;
        • Lemmens V.E.
        • Klaver Y.L.
        • Verwaal V.J.
        • Rutten H.J.
        • Coebergh J.W.W.
        • De Hingh I.H.
        Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study.
        Int J Canc. 2011; 128: 2717-2725
        • Segelman J.
        • Granath F.
        • Holm T.
        • MacHado M.
        • Mahteme H.
        • Martling A.
        Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer.
        Br J Surg. 2012;
        • Glehen O.
        • Kwiatkowski F.
        • Sugarbaker P.H.
        • 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;
        • Yan T.D.
        • Black D.
        • Savady R.
        • Sugarbaker P.H.
        Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma.
        J Clin Oncol. 2006;
        • Verwaal V.J.
        • 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): 2426-2432
        • Razenberg L.G.E.M.
        • Lemmens V.E.P.P.
        • Verwaal V.J.
        • et al.
        Challenging the dogma of colorectal peritoneal metastases as an untreatable condition: results of a population-based study.
        Eur J Canc. 2016; 65: 113-120
        • Verwaal V.J.
        • 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;
        • Kuijpers A.M.J.
        • Aalbers A.G.J.
        • Nienhuijs S.W.
        • et al.
        Implementation of a standardized HIPEC protocol improves outcome for peritoneal malignancy.
        World J Surg. 2015;
        • Elias D.
        • Lefevre J.H.
        • Chevalier J.
        • et al.
        Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.
        J Clin Oncol. 2009;
        • Bushati M.
        • Rovers K.P.
        • Sommariva A.
        • et al.
        The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI).
        Eur J Surg Oncol. 2018;
        • Wisselink D.D.
        • Braakhuis L.L.F.
        • Gallo G.
        • et al.
        Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer.
        Crit Rev Oncol Hematol. 2019;
        • Yurttas C.
        • Hoffmann G.
        • Tolios A.
        • et al.
        Systematic review of variations in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis from colorectal cancer.
        J Clin Med. 2018;
        • Maciver A.H.
        • Al-Sukhni E.
        • Esquivel J.
        • Skitzki J.J.
        • Kane J.M.
        • Francescutti V.A.
        Current delivery of hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (CS/HIPEC) and perioperative practices: an international survey of high-volume surgeons.
        Ann Surg Oncol. 2017;
        • Esquivel J.
        • Sticca R.
        • Sugarbaker P.
        • et al.
        Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement.
        Ann Surg Oncol. 2007; 14: 128-133
        • Rovers K.P.
        • Simkens G.A.
        • Punt C.J.
        • van Dieren S.
        • Tanis P.J.
        • de Hingh I.H.
        Perioperative systemic therapy for resectable colorectal peritoneal metastases: sufficient evidence for its widespread use? A critical systematic review.
        Crit Rev Oncol Hematol. 2017;
        • Rovers K.P.
        • Bakkers C.
        • Simkens G.A.A.M.
        • et al.
        Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parralel-group, phase II-III, random.
        BMC Canc. 2019;
        • Kelly K.J.
        • Alsayadnasser M.
        • Vaida F.
        • et al.
        Does primary tumor side matter in patients with metastatic colon cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?.
        Ann Surg Oncol. 2019;
        • Quenet F.
        • Elias D.
        • Roca L.
        • et al.
        A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): prodige 7.
        J Clin Oncol. 2018;
        • Baratti D.
        • Kusamura S.
        • Azmi N.
        • Guaglio M.
        • Montenovo M.
        • Deraco M.
        Colorectal peritoneal metastases treated by perioperative systemic chemotherapy and cytoreductive surgery with or without mitomycin C-based HIPEC: a comparative study using the peritoneal surface disease severity score (PSDSS).
        Ann Surg Oncol. 2019;
        • van Eden W.J.
        • Kok N.F.M.
        • Woensdregt K.
        • Huitema A.D.R.
        • Boot H.
        • Aalbers A.G.J.
        Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC.
        Eur J Surg Oncol. 2018; 44: 220-227
        • Hompes D.
        • D'Hoore A.
        • Wolthuis A.
        • et al.
        The of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study.
        J Surg Oncol. 2014; 109: 527-532
        • Prada-Villaverde A.
        • Esquivel J.
        • Lowy A.M.
        • et al.
        The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery.
        J Surg Oncol. 2014; 110: 779-785
        • Leung V.
        • Huo Y.R.
        • Liauw W.
        • Morris D.L.
        Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis.
        Eur J Surg Oncol. 2017; 43: 144-149
        • Charrier T.
        • Passot G.
        • Peron J.
        • et al.
        Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy with oxaliplatin increases the risk of postoperative hemorrhagic complications: analysis of predictive factors.
        Ann Surg Oncol. 2016;