Liver Metastases

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Unlike most other malignancies, colorectal cancer has a potential to metastasise to an isolated distant site, of which the liver is the most common. These locoregional metastases may be treated with surgical or ablative procedures or hepatic arterial chemotherapy (HAC).

Only about 20% of patients presenting with liver metastases are suitable for surgical resection. An adequate response to chemotherapy in advanced col-orectal cancer with initially unresectable liver metastases may permit resection of the metastases and the 5-year survival rate is similar to that of initially resectable metastases. In a retrospective analysis of 701 patients with initially unresectable liver metastases, surgery with curative intent was performed in 35% of patients following FU-LV and OXA; the 5-year survival rate was 35% with long-term survival, similar to that in initially curative resection [33]. Liver resection seems associated with a poor outcome if there is tumour progression under chemotherapy and metastatic disease is not controlled prior to surgery [34].

HAC delivers high concentrations of cytotoxic agents directly to liver metastases with minimal systemic toxicities. Randomised trials comparing HAC with systemic chemotherapy have demonstrated superior response rates and times to hepatic progression for unresectable disease. A meta-analysis based on seven trials compared HAC with floxuridine (FUDR) vs. IVC with FUDR or FU vs. best supportive care: tumour response rate was 41% and 14% for patients allocated to HAC and IVC respectively (p<0.0001); survival analyses showed a statistically significant advantage for HAI compared with control when all the trials were taken into account (p=0.0009) but not when survival analysis was restricted to trials comparing HAC and IVC (p=0.14) [35].

A recent randomised trial compared HAI with the standard IV de Gramont regimen for patients with metastases confined to the liver. There is no evidence of advantage in overall survival (14.7 and 14.8 months) or progression-free survival (7.7 and 6.7

months). Thus, clinical use of this regimen cannot be recommended and other prospective clinical trials should be conducted to more definitively answer this question [36].

According to the clinical response rate and median survival obtained with the new systemic regimen, phase I and II studies of HAI with oxaliplatin or CPT-11 have already been published. They have demonstrated tolerability and an interesting efficacy in heavily pretreated patients [37, 38].

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