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Modulation of 5-FU/alpha-interferon with high-dose continuous infusion hydroxyurea
1Department of Oncology, Montefiore Medical Center/Albert Einstein Cancer Center, Bronx, NY 10467.
The Journal of Infusional Chemotherapy
|January 1, 1995
Summary
Combining hydroxyurea with 5-fluorouracil (5-FU) chemotherapy shows promise for gastrointestinal cancers. Continuous hydroxyurea infusion may be key to achieving synergy with 5-FU and alpha-interferon (IFN) in clinical settings.
Area of Science:
- Oncology
- Pharmacology
- Gastrointestinal Malignancies
Background:
- Biochemically modulated 5-fluorouracil (5-FU) regimens demonstrate efficacy in treating gastrointestinal cancers.
- Hydroxyurea, a ribonucleotide reductase inhibitor, has shown synergistic potential with 5-FU in vitro.
- Previous clinical trials combining oral hydroxyurea with 5-FU have not yielded significant synergy.
Purpose of the Study:
- To review the pharmacology of hydroxyurea.
- To explore the rationale for modulating 5-FU/alpha-interferon (IFN) regimens with continuous infusion hydroxyurea.
- To investigate the potential for enhanced anti-cancer activity in gastrointestinal malignancies.
Main Methods:
- Review of existing pharmacological data on hydroxyurea.
- Analysis of pharmacokinetic properties of hydroxyurea related to continuous exposure.
- Examination of in vitro and clinical study outcomes for 5-FU and hydroxyurea combinations.
Main Results:
- In vitro studies suggest synergy between hydroxyurea and 5-FU.
- Clinical trials with oral hydroxyurea have not confirmed this synergy.
- Pharmacokinetic data suggest continuous hydroxyurea exposure might be necessary for synergy.
Conclusions:
- Continuous high-dose infusion of hydroxyurea may be a viable strategy to achieve synergy with 5-FU/IFN regimens.
- This approach warrants further investigation for gastrointestinal malignancies.
- Understanding drug pharmacokinetics is crucial for optimizing combination cancer therapies.