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Randomized Trial of Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy Versus Systemic Chemotherapy and Palliative Surgery in Patients With Peritoneal Carcinomatosis of Colorectal Cancer

Vic J. Verwaal, Serge van Ruth, Eelco de Bree, Gooike W. van Slooten, Harm van Tinteren, Henk Boot, Frans A.N. Zoetmulder

From the Departments of Surgery, Biometrics, and Gastroenterology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.

Address reprint requests to Vic J. Verwaal, MD, Department of Surgery, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: v.verwaal{at}nki.nl.

Purpose: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin.

Patients and Methods: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival.

Results: After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P = .032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P < .0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P < .0001).

Conclusion: Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.

Supported with grant OG98-041 from Ontwikkelings Geneeskunde.

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Related Correspondence

• Intraperitoneal Hyperthermic Chemotherapy As Treatment of Peritoneal Carcinomatosis of Colorectal Cancer
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  JCO 2004 22: 1527 [Full Text]
• Hyperthermic Intraperitoneal Chemotherapy in Patients With Peritoneal Carcinosis
  Bert Hildebrandt, Beate Rau, Johanna Gellermann, Peter Wust, and Hanno Riess
  JCO 2004 22: 1527-1529 [Full Text]

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• In Reply:
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  JCO 2004 22: 1529 [Full Text]

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