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

S. C. Remick, A. B. Benson, J. L. Weese, J. K V Willson, G. Ramirez, G. W. Wirtanen, D. B. Alberti, L. M. Nieting, K. D. Tutsch, P. H. Fischer, D. L. Trump

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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 an 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 (≤0.1 μM). 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.

Original languageEnglish (US)
Pages (from-to)6437-6442
Number of pages6
JournalCancer Research
Volume49
Issue number22
Publication statusPublished - 1989

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Remick, S. C., Benson, A. B., Weese, J. L., Willson, J. K. V., Ramirez, G., Wirtanen, G. W., ... Trump, D. L. (1989). 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. Cancer Research, 49(22), 6437-6442.