Phase I trial of hepatic artery infusion of 5-iodo-2'-deoxyuridine and 5-fluorouracil in patients with advanced hepatic malignancy: biochemically based combination chemotherapy.

Abstract

Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8-14 of therapy, patients received IdUrd as a separate 3-h HAI daily x 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day x 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2'deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (less than or equal to 0.1 microM). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day x 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day x 7.

• Authors: S C Remick, A B Benson 3rd, J L Weese, J K Willson, G Ramirez, G W Wirtanen, D B Alberti, L M Nieting, K D Tutsch, P H Fischer
• Journal: Cancer research (Cancer Res) Vol. 49 Issue 22 Pg. 6437-42 (Nov 15 1989) ISSN: 0008-5472 [Print] United States
• PMID: 2804987 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Idoxuridine
• Fluorouracil

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Dogs
• Drug Evaluation
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Hepatic Artery
• Humans
• Idoxuridine (administration & dosage, adverse effects, blood)
• Infusions, Intra-Arterial
• Liver (drug effects, pathology)
• Liver Neoplasms (drug therapy, secondary)
• Male
• Middle Aged