Isolated Hepatic Perfusion for Colorectal Liver Metastases

Ershler, William B.
July 2008
Clinical Oncology Alert;Jul2008, Vol. 24 Issue 7, p53
Approximately one third of patients with advanced colon cancer have metastatic disease confined to the liver. The past decade has seen an expanded role for surgery in this setting, particularly if the number, location and size of the metastatic deposits allow complete resection. If not, radiofrequency ablation (RFA) and isolated hepatic perfusion (IHP) are alternative approaches that can provide aggressive local treatment while reducing systemic toxicity. Phase II studies involving IHP in colorectal cancer have shown hepatic response rates up to 74% with a median time to hepatic progression up to 14.5 months, a median overall survival of 27 months and a 5 year survival of 9%.3 van Iersel and colleagues from Leiden report on their experience with patients with liver metastases who underwent IHP with 200 mg melphalan to identify prognostic factors for local and systemic failure. Over a ten year period, 154 colorectal cancer patients with measurable, non-resectable metastatic disease confined to the liver underwent laparotomy for isolation of hepatic circulation for chemotherapy infusion. This complex procedure was conducted by use of extracorporeal bypass. Melphalan, 200 mg was administered either as a bolus or a 20 minute infusion in the isolated hepatic circuit. Post operatively, patients were observed in the intensive care unit for a minimum of one day and received antibiotics and granulocyte colony stimulating factor until their white blood count had risen to >1.0 x 109/L. Objective tumor response measurements were obtained by follow-up CT scans, initially at 3 month intervals. There were six deaths within 30 days of the procedure due to progressive liver failure, and another at 90 days because of hepatic abscess. Overall, 41 (39%) experienced grade 3 or 4 hepatotoxicity, which was transient in most, but not in those who developed veno-occlusive disease (n = 9) or portal hypertension (n = 2). Comparative CT scans revealed an hepatic response rate of 50% by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progression-free and overall survival were 7.4 and 24.8 months, respectively. Univariate analysis revealed that positive prognostic factors for hepatic response to IHP were female sex and the use of adjuvant systemic chemotherapy. Multivariate analysis confirmed the benefit of adjuvant chemotherapy (odds ratio for complete or partial remission, 5.91; 95% confidence interval [CI] 1.54-22.6; P = 0.009) whereas the effect of female sex was only marginally significant (odds ratio for complete or partial remission, 2.65; 95% CI 0,98-7.15; P = 0.05). Regarding overall survival, the absence of ability to perfuse through the hepatic artery (P = 0.003), severe postoperative complications (P = 0.048) and >10 liver metastases (P = 0.006) were independent adverse factors, whereas not using adjuvant chemotherapy adversely influenced progression-free survival P = 0.039.


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