This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frankfurt, O. S. Search for Related Content PubMed PubMed Citation Articles by Frankfurt, O. S.

Enhancement of the Antitumor Activity of 5-Fluorouracil by Drug Combinations

Laboratory of Experimental Oncology, Department of Kinetics of Chemical and Biological Processes, Institute of Chemical Physics, Moscow, V-334, U. S. S. R.

We planned the treatment of Ehrlich ascites tumor, taking into account the duration of cell-cycle phases and their sensitivity to various drugs. Two days after the inoculation of 10⁷ ascites tumor cells, mice were given one injection of different drug combinations and the tumor cell number was then counted. It was found that hydroxyurea enhanced the antitumor activity of 5-fluorouracil (5-FU). This effect was evident only when 5-FU was injected together with vinblastine or when 5-FU was injected twice with an interval close to the G₂ phase duration. Hydroxyurea alone had no effect on tumor growth. Important features of the enhancement of 5-FU activity by hydroxyurea were the cell death that was evident from the decrease in cell number and significant prolongation of proliferation inhibition. An additive action was demonstrated for 5-FU and vinblastine. Enhancement of the antitumor action by the drug combinations described was not accompanied by increased toxicity.

A combination of drugs that damage different phases of the cell cycle and the injection of drugs with a time interval sufficient for resistant cells to pass into the sensitive phase may prove to be useful.

Received 7/ 6/72. Accepted 1/31/73.

This article has been cited by other articles:

				A. Argiris, D. J. Haraf, M. S. Kies, and E. E. Vokes Intensive Concurrent Chemoradiotherapy for Head and Neck Cancer with 5-Fluorouracil- and Hydroxyurea-Based Regimens: Reversing a Pattern of Failure Oncologist, August 1, 2003; 8(4): 350 - 360. [Abstract] [Full Text] [PDF]

				S. Wadler, S. Damle, H. Haynes, R. Kaleya, R. Schechner, R. Berkenblit, R. D. Ladner, and A. Murgo Phase II/Pharmacodynamic Trial of Dose-Intensive, Weekly Parenteral Hydroxyurea and Fluorouracil Administered With Interferon Alfa-2a in Patients With Refractory Malignancies of the Gastrointestinal Tract J. Clin. Oncol., June 1, 1999; 17(6): 1771 - 1771. [Abstract] [Full Text] [PDF]