# Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer

Source: https://onco.cc/key-papers/paper-verwaal-cytoreduction-hipec-peritoneal-colorectal-jco-2003/  
OnCo record `paper-verwaal-cytoreduction-hipec-peritoneal-colorectal-jco-2003` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The Dutch trial that put heated chemotherapy into the abdomen after stripping out all visible tumour, and nearly doubled median survival from 12.6 to 22.3 months. Eight percent of patients died of the treatment.

## Summary

Verwaal, van Ruth, de Bree and colleagues randomly assigned 105 patients between February 1998 and August 2001 to standard treatment (systemic fluorouracil-leucovorin with or without palliative surgery) or to aggressive cytoreduction with hyperthermic intraperitoneal chemotherapy followed by the same systemic regimen. The primary end point was survival.

Subgroup analysis showed that patients with fewer regions of the abdominal cavity involved, and those in whom cytoreduction was macroscopically complete, did far better, which is the selection principle every peritoneal service has used since.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: Journal of Clinical Oncology
- Year: 2003
- DOI: 10.1200/JCO.2003.04.187
- Authors: Verwaal VJ, van Ruth S, de Bree E, et al.
- Findings: After a median 21.6 months, median survival 12.6 months with standard treatment against 22.3 months with cytoreduction plus hyperthermic intraperitoneal chemotherapy (log-rank p=0.032).; Treatment-related mortality in the aggressive therapy group 8 percent, with most complications related to bowel leakage.; Patients with 0 to 5 of seven abdominal regions involved survived significantly longer than those with 6 or 7 (p<0.0001).; Macroscopically complete cytoreduction was associated with significantly better survival than limited or extensive residual disease (p<0.0001).
- What it means: The trial that created peritoneal surface malignancy as a speciality, and the reason patients with limited peritoneal disease are referred to designated centres; PRODIGE 7 later showed the benefit belongs to the surgery, not to the heated chemotherapy.
- Caveats: 105 patients, and the control arm received fluorouracil-leucovorin alone, a standard superseded within two years by oxaliplatin and irinotecan combinations.; 8 percent treatment-related mortality.; The trial could not separate the contribution of the cytoreduction from that of the intraperitoneal chemotherapy, which is the question PRODIGE 7 was designed to answer.

## Sources

- J Clin Oncol 2003: https://doi.org/10.1200/JCO.2003.04.187
- PubMed: https://pubmed.ncbi.nlm.nih.gov/14551293/

## Connected records

- key papers: [Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7)](https://onco.cc/key-papers/paper-quenet-prodige-7-hipec-peritoneal-colorectal-lancet-oncol-2021/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Surgery & Interventional](https://onco.cc/fronts/surgery/)
- technologies: [HIPEC / PIPAC (intraperitoneal chemotherapy)](https://onco.cc/technologies/hipec/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Leucovorin (folinic acid)](https://onco.cc/drugs/leucovorin/)
- institutions: [Netherlands Cancer Institute (NKI-AvL)](https://onco.cc/institutions/nki/)
- bottlenecks: [Fragmented care and guideline gaps](https://onco.cc/bottlenecks/b-care-fragmentation/), [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- ideas: [Find peritoneal spread while it is still small, and run complete cytoreduction through networks rather than adding heated chemotherapy](https://onco.cc/ideas/idea-crc-peritoneal-disease-found-early-and-treated-in-networks/)

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