Intrahepatic Chemotherapy

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The rationale for administering intrahepatic arterial chemotherapy is that by delivering chemotherapy directly to the target organ, high levels of drug will reach the metastatic lesions. As 5-FU undergoes arterial extraction at first pass the concentrations will be far greater (up to 100 times) than that obtained with intravenous administration. This will be of particular benefit due to the steep dose-response curve seen with cytotoxic drugs. However, the procedure is complex and potentially dangerous, requiring insertion of an intra-arterial catheter.

The meta-analysis Group in Cancer carried out a meta-analysis of early trials of intrahe-patic arterial (IHA) chemotherapy, using data from individual patients, reviewing response rates and survival rates (39). Their report revealed that IHA treatment gave improved objective tumor response rates when compared to intravenous therapy (IHA 41 vs. 14% IV or 0.25, 95% CI 0.16-0.40, p < 0.0001) but a statistically significant survival advantage was only found when the two of the seven included trials comparing IHA with physicians' choice of treatment were combined. In the other five trials comparing IHA with intravenous treatment no significant survival advantage was seen.

A more recent multicenter randomized trial (40) has been undertaken to investigate this further. A total of 290 patients were involved and were allocated to receive either intravenous chemotherapy (folinic acid 200 mg/m2, fluorouracil bolus 400 mg/m2 and 22-hour infusion 600 mg/m2, days 1 and 2, repeated every 14 days) or IHA designed to be equitoxic (folinic acid 200 mg/m2, fluorouracil 400 mg/m2 over 15 minutes and 22-hour infusion 1600 mg/m2, days 1 and 2, repeated every 14 days). The authors found that 50 (37%) of the patients allocated to IHA did not start their treatment and a further 39 (29%) had to stop before completing six cycles of treatment due to catheter failure (thrombosis, etc.). Median overall survival was 14.7 months for the IHA group and 14.8 months for the intravenous group (hazard ratio 1.04, 95% CI 0.80-1.33; log rank test P=0.79). There was no significant difference in PFS. The authors concluded that the IHA regimen could not be recommended outside the clinical trial setting.

There may also be no advantage for this route of administration for the newer agents in view of their differing pharmacodynamics. Irinotecan is a prodrug requiring activation to SN-38, hence HIA may not be appropriate. The role of oxaliplatin in this setting has yet to be established.

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