Tolerance to pituitary-adrenal axis activation by anticancer drugs in normal and tumour-bearing rats

Cisplatinum given intravenously (i.v.), hydroxyurea given orally (os), procarbazine (os) and L-asparaginase (i.v.), on a decreasing scale, produce significant (p less than 0.01) adrenocortical activation over 4-h period at a single dose per kg 10 times higher than those employed in human therapy. Only hydroxyurea retained this activity after a 5-day treatment both in normal and Walker carcinosarcoma-bearing rats. Adrenocortical activation depends on the presence of pituitary ACTH both after single or repeated treatments.