The growth of a number of cancers is hormone-dependent or regulated by hormones. Glucocorticoids are used for their antiproliferative and lympholytic properties and to ameliorate untoward responses to other treatments. Estrogen, androgen, and GnRH analogs and antagonists are effective in extending survival and delaying or preventing tumor recurrence of both breast and prostate cancer. These molecules interrupt the stimulatory axis created by systemic pools of androgens and estrogens, inhibit hormone production or hormone binding to receptors, and ultimately block expression of genes that promote tumor growth and survival.
The pharmacology, major therapeutic uses, and toxic effects of the glucocorticoids are discussed in Chapter 42. Only the applications of these drugs in the treatment of neoplastic disease are considered here.
Glucocorticoids act by binding to a specific physiological receptor that translocates to the nucleus and induces antiproliferative and apoptotic responses in sensitive cells. Because of their lympholytic effects and their ability to suppress mitosis in lymphocytes, glucocorticoids are used as cytotoxic agents in the treatment of acute leukemia in children and malignant lymphoma in children and adults. In acute lymphoblastic or undifferentiated leukemia of childhood, glucocorticoids may produce prompt clinical improvement and objective hematological remissions in ≤30% of children. However, the duration of remission is brief. Remissions occur more rapidly with glucocorticoids than with antimetabolites, and there is no evidence of cross-resistance to unrelated agents. Thus, therapy is initiated with prednisone and vincristine, often followed by an anthracycline or methotrexate, and l-asparaginase. Glucocorticoids are a valuable component of curative regimens for other lymphoid malignancies, including Hodgkin disease, non-Hodgkin lymphoma, multiple myeloma, and chronic lymphocytic leukemia (CLL). Glucocorticoids are extremely helpful in controlling autoimmune hemolytic anemia and thrombocytopenia associated with CLL.
A number of glucocorticoids are available and at equivalent dosages exert similar effects (see Chapter 42). Prednisone, e.g., usually is administered orally in doses as high as 60-100 mg, for the first few days and gradually reduced to levels of 20-40 mg/day, using the lowest possible effective dose. Side effects of these agents include glucose intolerance, immunosuppression, osteoporosis, and psychosis (see Chapter 42). Dexamethasone is the preferred agent for remission induction in multiple myeloma, usually in combination with melphalan, anthracyclines, vincristine, bortezomib, or thalidomide. Glucocorticoids, particularly dexamethasone, are used in conjunction with radiotherapy to reduce edema related to tumors in critical areas such as the superior mediastinum, brain, and spinal cord. Doses of 4-6 mg every 6 h have dramatic effects in restoring neurological function in patients with cerebral metastases, but these effects are temporary. Acute changes in dexamethasone dosage can lead to a rapid recrudescence of symptoms. Dexamethasone should not be discontinued abruptly in patients receiving radiotherapy or chemotherapy for brain metastases.
Progestational agents (see Chapters 40 and 66) are used as second-line hormonal therapy for metastatic hormone-dependent ...