A Note on Treatment Regimens
Cancer treatment regimens change to reflect continuous advances in basic and clinical science: new drugs, both small molecules and biologicals; improved methods of targeting and timing of drug delivery; agents with altered pharmacokinetic properties and selectivities; the use of rational multidrug combinations; and greater knowledge of the basic cell biology of tumorigenesis, metastasis, and immune function, amongst other advances. As a consequence, this chapter presents relatively few detailed treatment regimens; rather, we refer the reader to the web-based resources of the U.S. FDA and the NCCN. Table 67–1 provides the details and demonstrates the complexities of treatment of two cancers.
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 and androgen antagonists, steroid synthesis inhibitors, and GnRH analogues and antagonists are all 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.
ADME: absorption, distribution, metabolism, excretion
ADT: androgen deprivation therapy
AI: aromatase inhibitor
ALL: acute lymphoblastic leukemia
AR: androgen receptor
CDK: cyclin-dependent kinase
CLL: chronic lymphocytic leukemia
CRPC: castration-resistant prostate cancer
CYP: cytochrome P450
ER: estrogen receptor
ERE: estrogen-response element
FDA: Food and Drug Administration
FSH: follicle-stimulating hormone
HL: Hodgkin lymphoma
HR: hormone receptor
GnRH: gonadotropin-releasing hormone
GR: glucocorticoid receptor
HR: hormone receptor (i.e., ER+/PR+)
LH: luteinizing hormone
MM: multiple myeloma
mTOR: mechanistic target of rapamycin
NCCN: National Comprehensive Cancer Network
NHL: non-Hodgkin lymphoma
PR: progesterone receptor
PSA: prostate-specific antigen
SERD: selective estrogen receptor downregulator
SERM: selective estrogen receptor modulator
DRUGS THAT TARGET THE GLUCOCORTICOID RECEPTOR
The pharmacology, major therapeutic uses, and toxic effects of the glucocorticoids are discussed in Chapter 46. Only the applications of these drugs in the treatment of neoplastic disease are considered here.
Glucocorticoids act by binding to a specific GR that is a member of the nuclear receptor family of transcription factors. The GR translocates to the nucleus and induces complex gene expression changes (Chapter 46) that lead to 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 ...