# CROSS-RESISTANCE OR SENSITIVITY IN MULTIMODAL THERAPY

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1988 · $126,302

## Abstract

Marked improvement in tumor cure rates can be achieved by the alternation
of cyclophosphamide (CP) with intermittent multiple fractions per day (MFD)
radiation schedules compared to the alternating of CP with daily fraction
schedules in the ACI rat using hepatoma 3924A.  A cure rate of 50% was
achieved with 6000 rad intermittent MFD alternated with CP contrasted with
11,250 rad with daily radiation fractions and CP.  There were no cures with
sequential (LD10) doses of 150 mg/kg (0.9 g/m2) CP every 11 days for bone
marrow recovery for 2,3,4 and 5 courses (total doses of 300-750 mg/kg CP).
If the radiation was concentrated over a 2-day period as MFD and given
every 11 days for 3 courses, no tumor cures were demonstrated over a
radiation dose range of 3000-9000 rad.  The effects of daily radiation
schedules over a dose range of 3000-11,250 rad demonstrated no tumor
cures.  However, it was possible to achieve a greater than 50% cure rate
for the primary tumor and eliminate metastatic dissemination with
acceptable limits of toxicity with intermittent MFD radiation alternated
with CP.  Furthermore, this was not possible with daily radiation schedules
alternated with CP.  New therapeutic approaches to improving cancer
treatment will likely be coordinated with either single or combined
chemotherapy-radiotherapy.  The results of our experimental studies
demonstrate the potential for improvements in cancer management by more
effectively utilizing radiotherapy and chemotherapy.  We propose to extend
our studies by looking for development of resistance to other
chemotherapeutic agents (cis-platinum, adriamycin and 5-fluorouracil) and
for cross resistance or cross sensitivity with these drugs and radiation.
These studies will be carried out in tumor line 3924A shown to be
responsive to both radiation and the agents to be evaluated and in tumor
line H-4-II-E shown to be resistant to radiation and the agents to be
evaluated (neither the sensitivity nor the resistance of cis-platinum has
been evaluated).  These drugs were chosen for study because of their
widespread clinical use and proven effectiveness.  We believe that
extending our studies to include these other drugs is justified by 1) the
success with alternating chemotherapy and radiotherapy experimentally; 2)
its promising clinical application to treatment of lung cancer, head and
neck cancer and Hodgkin's disease; 3) the clinical studies planned or in
progress in this country, Europe and South Africa alternating chemotherapy
and radiotherapy in the treatment of cancer of the cervix, ovary,
anal-rectal region, pancreas and non-Hodgkin's lymphoma; and 4) the
continued clinical problem of development of drug resistance for these and
other agents.

## Key facts

- **NIH application ID:** 3172967
- **Project number:** 5R01CA035372-06
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** WILLIAM B. LOONEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $126,302
- **Award type:** 5
- **Project period:** 1983-07-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172967

## Citation

> US National Institutes of Health, RePORTER application 3172967, CROSS-RESISTANCE OR SENSITIVITY IN MULTIMODAL THERAPY (5R01CA035372-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172967. Licensed CC0.

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