Hepatic arterial chemotherapy for colorectal cancer liver metastases: a review of advances in 2003.

Abstract

During 2003, two new randomized trials comparing fluoropyrimidine-based hepatic arterial chemotherapy (HAC) with systemic chemotherapy were published. These new data will be reviewed in the context of previous trials and new observations of novel approaches involving HAC. The large Medical Research Council (MRC)/European Organization for the Research and Treatment of Cancer (EORTC) and the smaller Cancer and Leukaemia Group B (CALGB) trials reported conflicting conclusions. Lack of difference in response rates and survival outcomes was noted by the European trial groups whereas the contrary was reported by the US investigators, with statistically significant difference in response rates of 48% and 25% and median survival of 22.7 months and 19.8 months, respectively, being observed, favoring HAC. Early studies testing incorporation of irinotecan or oxaliplatin into HAC, either as additional systemic chemotherapy or as integral components of the HAC infusional regimen, confirmed feasibility, safety, and efficacy, with response rates between 30% and 60% being reported in some series. Other studies showed that combination with internal irradiation with lipiodol I-131 and biologic agents, eg, replication-selective adenovirus and cytokines, could be achieved with tolerable toxicity. Molecular prognostic factors that may help tailor treatment for individual patients were being investigated and low expression of thymidylate synthase (TS) and p21 was shown to correlate with better outcome, whereas patients with positive TS seemed to derive more benefit from HAC plus systemic chemotherapy than systemic chemotherapy alone. These studies confirmed that fluoropyrimidine-based HAC cannot be recommended routinely outside clinical trial as yet, but this treatment has its own merits and will continue to evolve with the availability of novel chemotherapeutic and biologic agents. Further studies into molecular prognostic factors will eventually define the role of HAC by selecting the right drug and the best route of administration for an individual patient.