title: Regional hepatic arterial infusion of degradable starch microspheres increases fluorodeoxyuridine (FUdR) tumor uptake.
abstract: 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.
authors.affiliation: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: A K
authors.initials: AK
authors.lastname: Thom
authors.forename: E R
authors.initials: ER
authors.lastname: Sigurdson
authors.forename: M
authors.initials: M
authors.lastname: Bitar
authors.forename: J M
authors.initials: JM
authors.lastname: Daly
mesh_terms: D000368:Aged; D005260:Female; D005467:Floxuridine / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006498:Hepatectomy; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D008099:Liver / Q000032:analysis / Q000378:metabolism; D008102:Liver Circulation; D008113:Liver Neoplasms / Q000032:analysis / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D013213:Starch / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D005467:Floxuridine; D013213:Starch