{"entity":{"id":"netherlands-hipec","kind":"trial","name":"Netherlands Cancer Institute HIPEC trial","aka":["Verwaal trial"],"tldr":"The trial that made cytoreductive surgery with a heated chemotherapy wash a treatment rather than an experiment. Twenty years later PRODIGE 7 showed the surgery, not the wash, was doing the work.","summary":"Verwaal and colleagues at the Netherlands Cancer Institute randomised 105 patients with peritoneal carcinomatosis of colorectal origin to cytoreductive surgery with mitomycin C hyperthermic intraperitoneal chemotherapy followed by systemic fluorouracil and leucovorin, or to systemic fluorouracil and leucovorin with palliative surgery when needed. Median survival was 22.3 against 12.6 months (p=0.032) after a median 21.6 months of follow-up. Treatment-related mortality in the aggressive arm was 8 percent, most complications coming from bowel leakage, and patients with six or seven of the seven abdominal regions involved, or an incomplete cytoreduction, did badly. This trial created the specialist peritoneal surface malignancy services that exist today. PRODIGE 7 later showed that oxaliplatin HIPEC adds nothing to complete cytoreduction, so what this trial really demonstrated is the value of the operation and of selecting patients with limited disease.","status":"positive","asOf":"2026-09-24","links":[{"label":"Verwaal: randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in peritoneal carcinomatosis of colorectal cancer (Journal of Clinical Oncology 2003)","url":"https://doi.org/10.1200/JCO.2003.04.187"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["hipec","hipec-pipac-devices"],"targets":[],"drugs":["mitomycin","fluorouracil","leucovorin"],"companies":[],"institutions":["nki"],"pathways":[],"terms":["debulking"],"trials":["prodige-7","colopec","prophylochip"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"phase":"3","setting":"Peritoneal carcinomatosis from colorectal cancer: cytoreductive surgery with mitomycin C hyperthermic intraperitoneal chemotherapy and systemic fluorouracil and leucovorin, against systemic fluorouracil and leucovorin with or without palliative surgery","sponsor":"Netherlands Cancer Institute","result":"Median survival 22.3 against 12.6 months (p=0.032), with 8 percent treatment-related mortality.","yearReported":2003,"enrolled":105,"enrolledBasis":"randomised","enrolledNote":"105 patients were randomised between 1998 and 2001; the trial predates the registries.","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Cytoreductive surgery plus mitomycin HIPEC and systemic chemotherapy","value":22.3},{"name":"Systemic chemotherapy with or without palliative surgery","value":12.6}],"p":"0.032","source":"https://doi.org/10.1200/JCO.2003.04.187"}],"replication":"PRODIGE 7 found no survival gain from adding oxaliplatin HIPEC to complete cytoreduction (41.7 against 41.2 months), and COLOPEC and PROPHYLOCHIP were negative as prophylaxis."},"route":"/trials/netherlands-hipec/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"hipec","kind":"technology","name":"HIPEC / PIPAC (intraperitoneal chemotherapy)","route":"/technologies/hipec/"},{"id":"hipec-pipac-devices","kind":"technology","name":"HIPEC perfusion pumps and PIPAC nebulisers","route":"/technologies/hipec-pipac-devices/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"leucovorin","kind":"drug","name":"Leucovorin (folinic acid)","route":"/drugs/leucovorin/"},{"id":"mitomycin","kind":"drug","name":"Mitomycin C","route":"/drugs/mitomycin/"}],"institution":[{"id":"nki","kind":"institution","name":"Netherlands Cancer Institute (NKI-AvL)","route":"/institutions/nki/"}],"term":[{"id":"debulking","kind":"term","name":"Debulking (cytoreductive surgery)","route":"/terms/debulking/"}],"trial":[{"id":"colopec","kind":"trial","name":"COLOPEC","route":"/trials/colopec/"},{"id":"prodige-7","kind":"trial","name":"PRODIGE 7","route":"/trials/prodige-7/"},{"id":"prophylochip","kind":"trial","name":"PROPHYLOCHIP-PRODIGE 15","route":"/trials/prophylochip/"}]}}