Annals of Surgical Oncology

, Volume 14, Issue 6, pp 1818–1824 | Cite as

Optimization of Hyperthermic Intraperitoneal Chemotherapy With Oxaliplatin Plus Irinotecan at 43°C After Compete Cytoreductive Surgery: Mortality and Morbidity in 106 Consecutive Patients

  • Dominique Elias
  • Diane Goere
  • François Blot
  • Valérie Billard
  • Marc Pocard
  • Niaz Kohneh-Shahri
  • Bruno Raynard
Hepatic and Pancreatic Tumors



Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0–R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43°C.


A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43°C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy.


Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001).


This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.


Morbidity Mortality Peritoneal carcinomatosis Intraperitoneal chemotherapy Hyperthermia Cytoreductive surgery Oxaliplatin Irinotecan 



We acknowledge Lorna Saint Ange for editing.


  1. 1.
    Sugarbaker PH, Cuniffe W, Belliveau JF, de Bruin E, Graves T. Rationale for perioperative intraperitoneal chemotherapy as a surgical adjuvant for gastrointestinal malignancy. Reg Cancer Treat 1988;1:66–79Google Scholar
  2. 2.
    Sugarbaker PH, Schellinx ME, Chang D, Koslowe P, von Meyerfeldt M. Peritoneal carcinomatosis from adenocarcinoma of the colon. World J Surg 1996;20:585–92PubMedCrossRefGoogle Scholar
  3. 3.
    Fujimoto S, Shresta RD, Kokubun M, et al. Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far advanced gastric cancer. Ann Surg 1990;212:592–6PubMedCrossRefGoogle Scholar
  4. 4.
    Elias D, Blot F, El Otmany A, et al. Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy. Cancer 2001;92:71–6PubMedCrossRefGoogle Scholar
  5. 5.
    Los G, Mutsaers PH, van der Vijgh WJ, Baldew GS, de Graaf PW, McVie JG. Direct diffusion of cisplatinum in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy. Cancer Res 1989;48:3380–4Google Scholar
  6. 6.
    Zoetmulder FA. Cancer cell seeding during abdominal surgery: experimental studies. In: Sugarbaker PH, ed. Peritoneal Carcinomatosis: Principles of Management. Boston: Kluwer Acadademic Publishers, 1996:155–62Google Scholar
  7. 7.
    Jacquet P, Elias D, Sugarbaker P. L’implantation tumorale dans les sites de cicatrisation après chirurgie des cancers digestifs. J Chir (Paris) 1996;133:175–82Google Scholar
  8. 8.
    Elias D, Ouellet JF. Intraperitoneal chemohyperthermia. Rationale, technique, indications and results. Surg Oncol Clin N Am 2001;10:915–33PubMedGoogle Scholar
  9. 9.
    Ceelen WP, Hesse U, de Hemptinne B, Pattyn P. Hyperthermic intraperitoneal chemoperfusion in the treatment of locally advanced intra-abdominal cancer. Br J Surg 2000;87:1006–15PubMedCrossRefGoogle Scholar
  10. 10.
    Rietbroeck RC, van de Vaart PJ, Haveman J, et al. Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells. J Cancer Res Clin Oncol 1997;123:6–12CrossRefGoogle Scholar
  11. 11.
    Elias D, Raynard B, Farkhondeh F, et al. Peritoneal carcinomatosis of colorectal origin: long-term results of intraperitoneal chemohyperthermia with oxaliplatin following complete cytoreductive surgery. Gastroenterol Clin Biol 2006;30:1200–4PubMedGoogle Scholar
  12. 12.
    Becouarn Y, Ychou M, Ducreux M, et al. Phase II trial of oxaliplatin as first line chemotherapy in metastatic colorectal cancer. J Clin Oncol 1998;16:2739–44PubMedGoogle Scholar
  13. 13.
    Giachetti S, Perpoint B, Zidani R, et al. Phase III multicenter randomized trial of oxaliplatin added to chronomoduled fluorouracil-leucovorin as first line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18:136–47Google Scholar
  14. 14.
    De Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938–47PubMedGoogle Scholar
  15. 15.
    Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol 1998;14:254–61PubMedCrossRefGoogle Scholar
  16. 16.
    Yonemura Y, Fujimura T, Nishimura G, et al. Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination. Surgery 1996;119:437–44PubMedCrossRefGoogle Scholar
  17. 17.
    Elias D, Antoun A, Goharin A, et al. Research on the best chemohyperthermia technique for treatment of peritoneal carcinomatosis after complete resection. Int J Surg Invest 2000;1:431–9Google Scholar
  18. 18.
    Elias D, Bonnay M, Puizillou JM, et al. Heated intraoperative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol 2002;13:267–72PubMedCrossRefGoogle Scholar
  19. 19.
    Le Page S, Kwiatkowski F, Paulin C, et al. In vitro thermochemotherapy of colon cancer cell lines with irinotecan alone and combined with mitomycin C. Hepatogastroenterology 2006;53:693–7PubMedGoogle Scholar
  20. 20.
    Rougier P, van Custem E, Bajetta E, et al. Randomized trial of irinotecan versus flourouracyl by continuous infusion after fluouracyl failure in patients with metastatic colorectal cancer. Lancet 1998;352:1407–12PubMedCrossRefGoogle Scholar
  21. 21.
    Hribaschek A, Pross M, Kuhn R, et al. Prevention and treatment of peritoneal carcinomatosis in experimental investigations with CPT-11 or oxaliplatin. Anti-Cancer Drugs 2002;13:605–14PubMedCrossRefGoogle Scholar
  22. 22.
    Elias D, Matsuhisa T, Sideris L, et al. Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance. Ann Oncol 2004;15:1558–65PubMedCrossRefGoogle Scholar
  23. 23.
    Elias D, Dube P, Bonvalot S, et al. A treatment of liver metastases with moderate peritoneal carcinomatosis by hepatectomy and cytoreductive surgery followed by immediate postoperative intraperitoneal chemotherapy. Feasibility and preliminary results. Hepatogastroenterology 1999;46:360–3PubMedGoogle Scholar
  24. 24.
    Elias D, Delperro JR, Sideris L, et al. Treatment of peritoneal carcinomatosis from colorectal cancer: impact of the complete cytoreductive surgery and difficulties in conducting randomized trials. Ann Surg Oncol 2004;11:518–21PubMedCrossRefGoogle Scholar
  25. 25.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg 1995;221:29–42PubMedCrossRefGoogle Scholar
  26. 26.
    Sugarbaker PH, Stuart OA, Carmignani CP. Pharmacokinetics changes induced by the volume of chemotherapy solution in patients treated with hyperthermic intraperitoneal mitomycin C. Cancer Chemother Pharmacol 2006;57:703–8PubMedCrossRefGoogle Scholar
  27. 27.
    Martin RC, Brennan MF, Jacques DP. Quality of complication reporting in the surgical literature. Ann Surg 2002;235:803–13PubMedCrossRefGoogle Scholar
  28. 28.
    Verwaal V, 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;21:3737–43PubMedCrossRefGoogle Scholar
  29. 29.
    Glehen O, Kwiatowsky F, Sugarbaker P, et al. Cytoreductive surgery combined with intraperitoneal chemotherapy for management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 2004;22:3284–92PubMedCrossRefGoogle Scholar
  30. 30.
    Elias D, Delperro JR, Sideris L, et al. Treatment of peritoneal carcinomatosis from colorectal cancer: impact of the complete cytoreductive surgery and difficulties in conducting randomized trials. Ann Surg Oncol 2004;11:518–21PubMedCrossRefGoogle Scholar
  31. 31.
    Shimizu T, Maeta M, Koga S. Influence of local hyperthermia on the healing of small intestinal anastomosis in the rat. Br J Surg 1991;78:57–9PubMedCrossRefGoogle Scholar
  32. 32.
    Stephens AD, Alderman R, Chang D, et al. Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative chemotherapy using the coliseum technique. Ann Surg Oncol 1999;6:790–6PubMedCrossRefGoogle Scholar
  33. 33.
    Glehen O, Osinsky D, Cotte E, et al. Intraperitoneal chemohyperthermia using closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol 2003;10:863–9PubMedCrossRefGoogle Scholar
  34. 34.
    Smeenk RM, Verwaal VJ, Zoetmulder FA. Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei. A report of 103 procedures. Eur J Surg Oncol 2006;32:186–90PubMedCrossRefGoogle Scholar
  35. 35.
    Elias D, Raynard B, Boige V, et al. Impact of the extent and duration of cytoreductive surgery on postoperative haematological toxicity after intraperitoneal chemohyperthermia for peritoneal carcinomatosis. J Surg Oncol 2005;90:220–5PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Dominique Elias
    • 1
  • Diane Goere
    • 1
  • François Blot
    • 2
  • Valérie Billard
    • 3
  • Marc Pocard
    • 1
  • Niaz Kohneh-Shahri
    • 1
  • Bruno Raynard
    • 2
  1. 1.Department of Surgical OncologyInstitut Gustave RoussyVillejuifFrance
  2. 2.Intensive Care UnitInstitut Gustave RoussyVillejuifFrance
  3. 3.Department of AnesthesiologyInstitut Gustave RoussyVillejuifFrance

Personalised recommendations