Antitumour drug toxicity in pituitary or adrenal-ablated rats

Hypophysectomy or adrenalectomy increase the toxicity of the antitumour drug hydroxyurea (HYD) given by the oral route at daily doses/kg over 5 days, 10 times higher (10 Htd) than that employed in daily schedules for humans (100% and 85% lethality against 0% in intact controls). No differences were found between intact or hypophysectomized rats in their ability to tolerate a 5-day treatment with 1 Htd HYD given orally, 1-10 Htd of procarbazine (i.v.) and cisplatinum (i.v.) at a dose per kg/day equivalent to that recommended for protocols providing daily drug schedules in humans. L-asparaginase (10 Htd) induce 45% lethality in adrenalectomized animals. All the above drugs in intact rats induce significant (p less than 0.01) adrenocortical activation after single, and in the case of hydroxyurea after 5-days, treatment at the above dosages. Replacement therapy with corticosterone may reduce HYD toxicity in adrenalectomized (20% lethality) but less so (90% lethality) in hypophysectomized rats.