Annals of Surgical Oncology

, Volume 15, Issue 2, pp 535–541 | Cite as

Safety and Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with High-Dose Oxaliplatin in Patients with Peritoneal Carcinomatosis

  • Wim P. Ceelen
  • Marc Peeters
  • Philippe Houtmeyers
  • Christophe Breusegem
  • Filip De Somer
  • Piet Pattyn
Gastrointestinal Oncology



Cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma.


Following complete cytoreduction, HIPEC was performed using 460 mg/m2 oxaliplatin in 5% dextrose for 30 min at a temperature of 41–42°C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival.


From July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year.


Cytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival.


Peritoneal carcinomatosis Oxaliplatin HIPEC Chemotherapy Chemoperfusion 


  1. 1.
    Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354:34–43PubMedCrossRefGoogle Scholar
  2. 2.
    Flessner MF. The transport barrier in intraperitoneal therapy. Am J Physiol Renal Physiol 2005; 288:F433–F42PubMedCrossRefGoogle Scholar
  3. 3.
    Tannock IF, Lee CM, Tunggal JK, et al. Limited penetration of anticancer drugs through tumor tissue: A potential cause of resistance of solid tumors to chemotherapy. Clin Cancer Res 2002; 8:878–84PubMedGoogle Scholar
  4. 4.
    Verwaal VJ, 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
  5. 5.
    Yan TD, Black D, Savady R, et al. Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J Clin Oncol 2006; 24:4011–9PubMedCrossRefGoogle Scholar
  6. 6.
    van Ruth S, Mathot RAA, Sparidans RW, et al. Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy. Clin Pharmacokin 2004; 43:131–43CrossRefGoogle Scholar
  7. 7.
    Zeamari S, Floot B, Van der Vange N, et al. Pharmacokinetics and pharmacodynamics of cisplatin after Intraoperative Hyperthermic Intraperitoneal Chemoperfusion (HIPEC). Anticancer Res 2003; 23:1643–8PubMedGoogle Scholar
  8. 8.
    Los G, Vanvugt MJH, Pinedo HM. Response of peritoneal solid tumors after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin. Br J Cancer 1994; 69:235–41PubMedGoogle Scholar
  9. 9.
    Chau I, Cunningham D. Adjuvant therapy in colon cancer – what, when and how? Ann Oncol 2006; 17:1347–59PubMedCrossRefGoogle Scholar
  10. 10.
    Elkas JC, Winter WE, Chernofsky MR, et al. A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma. Gynecol Oncol 2007; 104:422–7PubMedCrossRefGoogle Scholar
  11. 11.
    Al-Batran SE, Atmaca A, Hegewisch-Becker S, et al. Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol 2004; 22:658–63PubMedCrossRefGoogle Scholar
  12. 12.
    Fennell DA, Steele JPC, Shamash J, et al. Phase II trial of vinorelbine and oxaliplatin as first-line therapy in malignant pleural mesothelioma. Lung Cancer 2005; 47:277–81PubMedCrossRefGoogle Scholar
  13. 13.
    Rietbroek RC, vandeVaart PJM, 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; 123:6–12PubMedCrossRefGoogle Scholar
  14. 14.
    Pestieau SR, Belliveau JF, Griffin H, et al. Pharmacokinetics of intraperitoneal oxaliplatin: Experimental studies. J Surg Oncol 2001; 76:106–14PubMedCrossRefGoogle Scholar
  15. 15.
    Elias D, Bonnay A, Puizillou JM, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: Pharmacokinetics and tissue distribution. Ann Oncol 2002; 13:267–72PubMedCrossRefGoogle Scholar
  16. 16.
    Jerremalm E, Hedeland M, Wallin I, et al. Oxaliplatin degradation in the presence of chloride: Identification and cytotoxicity of the monochloro monooxalato complex. Pharm Res 2004; 21:891–4PubMedCrossRefGoogle Scholar
  17. 17.
    Rubbia-Brandt L, Audard V, Sartoretti P, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004; 15:460–6PubMedCrossRefGoogle Scholar
  18. 18.
    Arotcarena R, Cales V, Berthelemy P, et al. Severe sinusoidal lesions: A serious and overlooked complication of oxaliplatin-containing chemotherapy? Gastroenterol Clin Biol 2006; 30:1313–6PubMedGoogle Scholar
  19. 19.
    Sugarbaker PH. Peritonectomy Procedures. Ann Surg 1995; 221:29–42PubMedCrossRefGoogle Scholar
  20. 20.
    Stephens AD, Alderman R, Chang D, et al. Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the Coliseum technique. Ann Surg Oncol 1999; 6:790–6PubMedCrossRefGoogle Scholar
  21. 21.
    Colevas AD, Setser A. The NCI Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 is the new standard for oncology clinical trials. J Clin Oncol 2004; 22:543SGoogle Scholar
  22. 22.
    Harnett P, Buck M, Beale P, et al. Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: An Australian and New Zealand Gynaecological Oncology Group study. Int J Gynecol Cancer 2007; 17:359–66PubMedCrossRefGoogle Scholar
  23. 23.
    Ceelen WP, Pahlman L, Mahteme H. Pharmacodynamic aspects of Intraperitoneal Cytotoxic therapy. In: Ceelen WP (ed) Peritoneal carcinomatosis: A multidisciplinary approach. New York, Springer; 2007. pp 195–214Google Scholar
  24. 24.
    Elias D, El Otmany A, Bonnay M, et al. Human pharmacokinetic study of heated intraperitoneal oxaliplatin in increasingly hypotonic solutions after complete resection of peritoneal carcinomatosis. Oncology 2002; 63:346–52PubMedCrossRefGoogle Scholar
  25. 25.
    Reed E. Cisplatin, Carboplatin, and Oxaliplatin. In: Chabner BA, Longo DL (eds) Cancer Chemotherapy & Biotherapy: Principles & Practices, 4th edition. Philadelphia: Lippincott Williams & Wilkins; 2006Google Scholar
  26. 26.
    Zorzi D, Laurent A, Pawlik TM, et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg 2007; 94:274–86PubMedCrossRefGoogle Scholar
  27. 27.
    Levi F, Metzger G, Massari C, Milano G. Oxaliplatin: pharmacokinetics and chronopharmacological aspects. Clin Pharmacokinet 2000; 38:1–21PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Wim P. Ceelen
    • 1
  • Marc Peeters
    • 2
  • Philippe Houtmeyers
    • 1
  • Christophe Breusegem
    • 1
  • Filip De Somer
    • 1
  • Piet Pattyn
    • 1
  1. 1.Departments of SurgeryGhent University HospitalGhentBelgium
  2. 2.Departments of GastroenterologyGhent University HospitalGhentBelgium

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