# CELLULAR PHARMACOLOGY IN CANCER CHEMOTHERAPY

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1989 · $119,780

## Abstract

The goal is to utilize an understanding of the metabolism and action of
antitumor drugs in cancer cells during chemotherapy to optimize the design
of treatment regimens for individuals and for specific hematologic
diseases.  Strong correlations have been established between the response
of patients with refractory acute leukemia to high-dose araC therapy and
the pharmacokinetics of the active metabolite araCTP in leukemic cells
during treatment.  These observations were confirmed prospectively and used
to design treatment protocols that utilize the cellular pharmacology of
araCTP a) to direct the intervals between intermittent doses of araC and b)
to indicate the rate of araC administration during a continuous infusion
regimen.  This application proposes to extend these studies in several
directions.  First, the cellular pharmacology of araCTP will be evaluated
with respect to the response of other hematologic malignancies to high-dose
araC to determine the scope of these findings.  Second, the cellular
metabolism and action of F-araAMP shares many similarities with araC.
Therefore, the cellular pharmacology of the active metabolite F-araATP will
be evaluated with respect to clinical response during Phase II trials.
Third, high-dose araC treatment will be combined with mitoxantrone and with
cisplatin to seek higher response rates.  This provides the opportunity to
determine whether the cellular pharmacology of araCTP continues to provide
independent prognostic information during combination chemotherapy, and to
investigate if these drugs affect araCTP metabolism.  Fourth, DNA damage
induced in leukemic cells during therapy with mitoxantrone or with
cisplatin will be quantitated by alkaline elution procedures coupled with
fluorescence detection.  The prognostic value of this evidence of drug
action will be evaluated.  Finally, knowledge gained in these studies of
the metabolism and action of antileukemic drugs in tumor cell during
therapy will be used to design new treatment protocols.

## Key facts

- **NIH application ID:** 3170686
- **Project number:** 5R01CA032839-07
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** WILLIAM K PLUNKETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $119,780
- **Award type:** 5
- **Project period:** 1983-08-01 → 1991-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170686

## Citation

> US National Institutes of Health, RePORTER application 3170686, CELLULAR PHARMACOLOGY IN CANCER CHEMOTHERAPY (5R01CA032839-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170686. Licensed CC0.

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