Anticancer Drug Toxicity in the Absence of Hypophyseal or Adrenal Secretion

Abstract

Regimes of treatment with cyclophosphamide-methotrexate-5-fluorouracil (CMF) or cyclophosphamide-adriamycin-5-fluorouracil(CAF) for breast cancer and 5-fluorouracil (5-FU) for prostate cancer may be used in patients with hormone-sensitive tumors after medical or surgical adrenalectomy or hypophy-sectomy (Craig-Henderson 1987). The anticancer drug hydroxyurea displayed a unique and marked toxicity in both pituitary- and adrenal-ablated animals (Vacca et al. 1985). The ability of intact, hypophysectomized, or adrenalectom-ized male adult rats to tolerate four anticancer drugs [busulfan (BU), carmustine (BCNU), cyclophosphamide (CY), and 5-FU] given according to the recommended treatment schedule and route in human cancer chemotherapy at doses corresponding to and 10–500 times greater than those employed per kilogram in humans (human therapeutic dose, Htd) (Salmon and Sartorelli 1987) was investigated. BU and BCNU are prescribed for neoplasm other than breast and prostate cancer but BU has caused “selective” pituitary insufficiency (Vivacqua et al. 1967) and BCNU may induce several hormonal changes due to pituitary stimulation (Kuo et al. 1975; Di Renzo et al. 1979).