Oxaliplatin versus Mitomycin C following complete cytoreduction for colorectal peritoneal metastases: a comparative study

  • Vignesh NarasimhanEmail author
  • Satish Warrier
  • Michael Michael
  • Robert Ramsay
  • Alexander Heriot
Original Article


Background and objectives

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with colorectal peritoneal metastases (CRPM) a favorable long-term survival. While cytoreductive techniques are standardized, there remains great variability in HIPEC drugs with mitomycin C or oxaliplatin use based largely on institute preference. In this study, we compared outcomes based on mitomycin C or oxaliplatin use after complete cytoreduction.


This is a retrospective analysis over a 7-year period of all patients undergoing complete cytoreduction with HIPEC.


Seventy-eight patients underwent complete cytoreduction with HIPEC during this time. Forty-six patients received oxaliplatin as HIPEC, and 32 received mitomycin C. There was no difference in patient characteristics, resections, or major morbidity between the two groups. Superficial wound infections were higher in the mitomycin C group (37.5% v 15.2%, p = 0.02). Median overall and disease-free survival for the entire cohort was 40 and 14 months, respectively. There was no difference in overall survival or disease-free survival between the two HIPEC groups (HR 0.50, 95% CI 0.11–2.28).


Complete cytoreduction and HIPEC can offer selected patients a favorable survival. The choice of mitomycin C or oxaliplatin for HIPEC had no influence on survival. Prospective studies are needed to explore this important issue.


Colorectal peritoneal metastases Peritonectomy Cytoreduction Hyperthermic intraperitoneal chemotherapy Oxaliplatin HIPEC 


Author Contribution

VN, SW, MM, RR, and AH produced the study concept and design. VN performed the scientific literature search. VN did the data collection and statistical analysis. All the authors were involved in refining the study design and data interpretation. VN, SW, MM, RR, and AH wrote the initial draft, with all the authors involved in the editing process and final version of the manuscript. All the authors have reviewed and approved the final manuscript. All the authors agree to be accountable for all aspects of the work.

Compliance with Ethical Standards

Peter MacCallum Cancer Centre institutional ethics was provided to conduct this comparative study.

Conflict of Interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2018;0:1-31.Google Scholar
  2. 2.
    AIHW. Australian Institute of Health and Welfare; Cancer in Australia 2017. Cancer series no. 101. Canberra2017.Google Scholar
  3. 3.
    Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018;36(8):773-9.CrossRefGoogle Scholar
  4. 4.
    Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT, et al. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016;17(12):1709-19.CrossRefGoogle Scholar
  5. 5.
    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(2):358-63.CrossRefGoogle Scholar
  6. 6.
    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;99(5):699-705.CrossRefGoogle Scholar
  7. 7.
    Lemmens V, Klaver Y, Verwaal V, Rutten H, Coebergh J, de Hingh I. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128(11):2717-25.CrossRefGoogle Scholar
  8. 8.
    Alzahrani NA, Valle SJ, Fisher OM, Sugarbaker PH, Yonemura Y, Glehen O, et al. Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience. J Surg Oncol. 2018.Google Scholar
  9. 9.
    Verwaal V, van Ruth S, de Bree E, van Slooten 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;21(20):3737-43.CrossRefGoogle Scholar
  10. 10.
    Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, 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;22(16):3284-92.CrossRefGoogle Scholar
  11. 11.
    Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681-5.CrossRefGoogle Scholar
  12. 12.
    Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, et al. 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.CrossRefGoogle Scholar
  13. 13.
    Goere D, Malka D, Tzanis D, Gava V, Boige V, Eveno C, et al. Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg. 2013;257(6):1065-71.CrossRefGoogle Scholar
  14. 14.
    Esquivel J, Lowy AM, Markman M, Chua T, Pelz J, Baratti D, et al. The American Society of Peritoneal Surface Malignancies (ASPSM) Multiinstitution Evaluation of the Peritoneal Surface Disease Severity Score (PSDSS) in 1,013 Patients with Colorectal Cancer with Peritoneal Carcinomatosis. Ann Surg Oncol. 2014;21(13):4195-201.CrossRefGoogle Scholar
  15. 15.
    Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-422.CrossRefGoogle Scholar
  16. 16.
    Li Y, Zhou Y, Liang H, Wang H, Hao J, Zhu Z, et al. Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies. World J Gastroenterol. 2016;22(30):6906-16.CrossRefGoogle Scholar
  17. 17.
    Klaver CE, Groenen H, Morton DG, Laurberg S, Bemelman WA, Tanis PJ, et al. Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines. Colorectal Dis. 2017;19(3):224-36.CrossRefGoogle Scholar
  18. 18.
    Vogel JD, Eskicioglu C, Weiser MR, Feingold DL, Steele SR. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Colon Cancer. Dis Colon Rectum. 2017;60(10):999-1017.CrossRefGoogle Scholar
  19. 19.
    Yurttas C, Hoffmann G, Tolios A, Haen SP, Schwab M, Konigsrainer I, et al. Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer. J Clin Med. 2018;7(12).Google Scholar
  20. 20.
    Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine E. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179(1):e133-9.CrossRefGoogle Scholar
  21. 21.
    van Eden WJ, Kok NFM, Woensdregt K, Huitema ADR, Boot H, Aalbers AGJ. 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(2):220-7.CrossRefGoogle Scholar
  22. 22.
    Quenet F, Elias D, Roca L, Goere D, Ghouti L, Pocard M, et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. J Clin Oncol. 2018;36(Suppl; abstr LBA3503).Google Scholar
  23. 23.
    Cavaliere F, De Simone M, Virzi S, Deraco M, Rossi CR, Garofalo A, et al. Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O. Eur J Surg Oncol. 2011;37(2):148-54.CrossRefGoogle Scholar
  24. 24.
    Goere D, Souadka A, Faron M, Cloutier A, Viana B, Honore C, et al. Extent of colorectal peritoneal carcinomatosis: attempt to define a threshold above which HIPEC does not offer survival benefit: a comparative study. Ann Surg Oncol. 2015;22(9):2958-64.CrossRefGoogle Scholar
  25. 25.
    Sugarbaker P. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 2005;7(1):69-76.CrossRefGoogle Scholar
  26. 26.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221(1):29-42.CrossRefGoogle Scholar
  27. 27.
    Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608-18.CrossRefGoogle Scholar
  28. 28.
    Ung L, Chua T, Morris D. Peritoneal metastases of lower gastrointestinal tract origin: a comparative study of patient outcomes following cytoreduction and intraperitoneal chemotherapy. J Cancer Res Clin Oncol. 2013;139:1899-908.CrossRefGoogle Scholar
  29. 29.
    Kozman M, Fisher O, Rebolledo B, Parikh R, Valle S, Arrowaili A, et al. CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy. J Surg Oncol. 2018;117:725-36.CrossRefGoogle Scholar
  30. 30.
    Ceelen W, Nieuwenhove Y, Putte D, Pattyn P. Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis. Ann Surg Oncol. 2014;21:3023-8.CrossRefGoogle Scholar
  31. 31.
    Elias D, Delperro J, Sideris L, Benhamou E, Pocard M, Baton O, et al. Treatment of peritoneal carcinomatosis from colorectal cancer: impact of complete cytoreductive surgery and difficulties in conducting randomized trials. Annals of Surgical Oncology. 2004;11(5):518-21.CrossRefGoogle Scholar
  32. 32.
    Hompes D, D'Hoore A, Wothuis A, Fieuws S, Mirck B, Bruin S, et al. The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol. 2014;109(6):527-32.CrossRefGoogle Scholar
  33. 33.
    Leung V, Huo Y, Liauw W, Morris D. Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43:144-9.CrossRefGoogle Scholar
  34. 34.
    Prada-Villaverde A, Esquivel J, Lowy A, Markman M, Chua T, Pelz J, 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;110:779-85.CrossRefGoogle Scholar
  35. 35.
    Rueth N, Murray S, Huddleston S, Abbott A, Greeno E, Kirstein M, et al. Severe Electrolyte Disturbances After Hyperthermic Intraperitoneal Chemotherapy: Oxaliplatin Versus Mitomycin C. Ann Surg Oncol. 2011;18:174-80.CrossRefGoogle Scholar
  36. 36.
    Atallah D, Marsaud V, Radanyi C, Kornprobst M, Rouzier R, Elias D, et al. Thermal enhancement of oxaliplatin-induced inhibition of cell proliferation and cell cycle progression in human carcinoma cell lines. Int J Hyperthermia. 2004;20(4):405-19.CrossRefGoogle Scholar
  37. 37.
    Kirstein MN, Root SA, Moore MM, Wieman KM, Williams BW, Jacobson PA, et al. Exposure-response relationships for oxaliplatin-treated colon cancer cells. Anticancer Drugs. 2008;19(1):37-44.CrossRefGoogle Scholar
  38. 38.
    Pinto A, Pocard M. Hyperthermic intraperitoneal chemotherapy with cisplatin and mitomycin C for colorectal cancer peritoneal metastases: A systematic review of the literature. Pleura Peritoneum. 2019;4(2):20190006.CrossRefGoogle Scholar
  39. 39.
    de Jong LAW, Elekonawo FMK, de Reuver PR, Bremers AJA, de Wilt JHW, Jansman FGA, et al. Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis: a clinical pharmacological perspective on a surgical procedure. Br J Clin Pharmacol. 2019;85(1):47-58.CrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  1. 1.Department of Surgical OncologyPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Sir Peter MacCallum Dept. of OncologyUniversity of MelbourneParkvilleAustralia
  3. 3.Department of Medical OncologyPeter MacCallum Cancer CentreMelbourneAustralia

Personalised recommendations