Hepatic
metastases of
colorectal carcinoma demonstrate a dose response to
chemotherapy. In animal studies hepatic arterial infusion of chemotherapeutic agents with
degradable starch microspheres (DSMs) produces a redistribution of blood flow between
tumor and liver and an increase in
tumor drug levels. In this prospective clinical study in patients with colorectal
metastases, we evaluated the effect of DSMs on liver and
tumor levels of fluoropyrimidines after intraoperative administration through the hepatic artery. Fourteen patients underwent infusion of radiolabeled
fluorodeoxyuridine, 14C-FUdR (0.15 mg/kg, 0.5 microCi/kg), followed 2 to 5 minutes later by infusion of 3H-FUdR (0.15 mg/kg, 1.0 microCi/kg) without (n = 3) or with (n = 11) DMS. Seven of the later patients underwent major hepatic resection and tissue mapping of
drug distribution, and four patients underwent biopsy procedures to remove specimens of liver and
tumor 5 minutes after
microsphere infusion. Administration of DSMs with
FUdR increased
tumor drug levels as measured by 3H-FUdR (5.9 +/- 4.4 vs 17.1 +/- 9.4 nmol/gm, p = 0.07) without altering hepatic
drug levels (35.7 +/- 10.9 vs 30.2 +/- 20.9 nmol/gm, p = NS) and significantly increased the
tumor/liver
drug ratio of tritiated fluoropyrimidines (0.16 +/- 0.09 to 0.63 +/- 0.13, p = 0.03). Fluoropyrimidine levels in
tumor and liver correlated with blood flow as measured by technetium-99m macroaggregated
albumin retention. Thus, hepatic arterial administration of DSMs in human beings enhances
tumor FUdR levels and may be useful in increasing
tumor cytotoxicity and decreasing systemic toxicity during regional hepatic infusion.