Allopurinol modification of the toxicity and antitumor activity of 5-fluorouracil
Schwartz, P.M.; Dunigan, J.M.; Marsh, J.C.; Handschumacher, R.E.
Cancer Research 40(6): 1885-1889
1980
ISSN/ISBN: 0008-5472 PMID: 7371020 Document Number: 157117
Allopurinol (HPP) reduced the mortality of 5-fluorouracil (FUra) to mice and rats by almost 2-fold. Toxic manifestations of FUra treatment, including weight loss, histological changes in the gastrointestinal mucosa and reduction of bone marrow cell survival, were lessened by prior and concomitant administration of HPP. In mice given a 7-day schedule of FUra (30 mg/kg per day), marrow cellularity was reduced; only 1% of the stem cells per femur survived compared to controls. This same schedule of FUra given with HPP (50 mg/kg per day), starting 1 day prior to and thereafter, 1 h before each FUra dose, caused less of a reduction in marrow cellularity; 17% of the stem cells in the femur survived compared to controls. The toxicity of FUra on mouse bone marrow cells was demonstrated in vitro as a reduction of the incorporation of solid colon tumor 38 cells. Increasing the dose schedule of FUra in combination with HPP did not increase the life span of P388-bearing mice beyond that seen with optimal schedules of FUra alone. In colon tumor 38-bearing mice, however, schedules of FUra given with HPP resulted in 100% greater delay in tumor growth than optimal schedules of FUra alone.