# HEPATIC TUMOR MICROCIRCULATION AND MICROSPHERE THERAPY

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1988 · $201,694

## Abstract

Liver involvement by cancer is a major source of morbidity and mortality.
The development of a totally implanted drug delivery system has rekindled
interest in hepatic arterial chemotherapy and generated a large patient
population amenable to studies aimed at more effective regional therapy.
Our recent studies in patients with liver cancer using tomographic nuclear
medicine scans after hepatic arterial injection of tracer microspheres
indicate that tumors are often hypervascular compared to normal liver.  Our
objective is to develop therapeutic approaches exploiting such potentially
selective differences between the microcirculation of hepatic tumors and
normal liver.  The ability of hepatic arterial infusion of vasoactive
agents (epinephrine, norepinephrine, angiotensin) to shunt blood flow and
microsphere delivery from normal liver to hepatic tumor nodules will be
examined.  Hepatic arterial administration of yttrium 90 microspheres will
be studied as a means to deliver internal radiotherapy and, the ability of
hepatic arterial infusion of bromodeoxyuridine (BUDR) to selectively
radiosensitize tumor to these microspheres will be explored.  Extensive
preclinical studies in rabbits bearing the VX2 tumor (intrahepatically
implanted) and in dogs will be used to rationally support the development
(and FDA approval) of invesstigational clinical protocols.  The rabbit
model will be used for vasoconstrictor regimen studies, to examine BUDR
pharmacodynamics, and to investigate comparative response to combined
therapies.  The dog will serve as a large animal model for pharmacokinetic
studies and to establish the relative toxicities of therapeutic regimens
combining hepatic arterial yttrium 90 microspheres with regional
radiosensitizer regimens.  Clinical efforts will consist of an initial
phase I study of yttrium 90 microspheres alone and then ultimately progress
to phase I studies of rational combinatins as directed by studies in the
preclinical models.  It is anticipated that the results of these
investigations will provide a basis for large scale randomized phase III
trials (in cooperative groups) as well as for the application of regional
radiosensitizer-radiotherapy regimens in the treatment of other
regionally-confined tumors such as head and neck cancer, brain tumors, and
tumors of the extremities.

## Key facts

- **NIH application ID:** 3171607
- **Project number:** 5R01CA033825-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** WILLIAM D ENSMINGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $201,694
- **Award type:** 5
- **Project period:** 1983-05-01 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171607

## Citation

> US National Institutes of Health, RePORTER application 3171607, HEPATIC TUMOR MICROCIRCULATION AND MICROSPHERE THERAPY (5R01CA033825-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171607. Licensed CC0.

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