++
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, among 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 (drugs@fda) and the NCCN (National Comprehensive Cancer Network). Table 71–1 provides the details and focuses on the complexities of treatment of two cancers.
++
Abbreviations
ADT: androgen deprivation therapy
AI: aromatase inhibitor
ALL: acute lymphoblastic leukemia
AR: androgen receptor
AUC: area under the curve
BAT: bipolar androgen deprivation therapy
BCRP: breast cancer resistance protein
CDK: cyclin-dependent kinase
CLL: chronic lymphocytic leukemia
CRPC: castration-resistant prostate cancer
CYP: cytochrome P450
ER: estrogen receptor
ERE: estrogen-response element
FSH: follicle-stimulating hormone
GnRH: gonadotropin-releasing hormone
GR: glucocorticoid receptor
HER: human epidermal growth factor
HL: Hodgkin lymphoma
HR: hormone receptor
LH(RH): luteinizing hormone (–releasing hormone)
MM: multiple myeloma
mTOR: mechanistic (or mammalian) target of rapamycin
NHL: non-Hodgkin lymphoma
OATP: organic anion transporting polypeptide
Pgp: P-glycoprotein
PR: progesterone receptor
PROTAC: proteolysis targeting chimeras
SERD: selective estrogen receptor downregulator
SERM: selective estrogen receptor modulator
UGT: UDP-glucuronosyltransferase
+++
INTRODUCTION TO HORMONE-REGULATED CANCERS
++
The growth of a number of cancers is hormone-dependent or regulated by hormones. Therapies that employ estrogen and androgen receptor antagonists, steroid hormone synthesis inhibitors, and gonadotropin-releasing hormone (GnRH) analogues or antagonists extend survival and delay or prevent tumor recurrence of both breast and prostate cancer. These molecules interrupt the normal feedback controls regulating steroid hormone synthesis, inhibit androgen and estrogen production, or inhibit binding of these hormones to their cognate receptors, which are ligand-activated transcription factors. By inhibiting the activation and actions of androgen and estrogen receptors, these drugs block or reduce expression of genes and gene networks that ultimately promote tumor growth and survival. Glucocorticoids are used for their antiproliferative and lympholytic properties in hematologic malignancies and, in other oncological settings, to mitigate untoward responses to other treatments as well as some cancer-related symptoms.
++
The pharmacology of the estrogens and androgens is described in detail in Chapters 48 and 49. Decreasing the actions of these steroid hormones is the therapeutic goal in certain cancers, most notably those of the prostate and breast, because these organs are dependent on steroid hormones for their growth, function, and morphological integrity.
+++
ENDOCRINE THERAPY OF BREAST CANCER
++
The presence of the estrogen receptor (ER) and/or progesterone receptor (PR) (ER+/PR+) in female breast cancer tissue identifies the subset of hormone receptor–positive cancers with a greater than 60% likelihood of responding to endocrine therapy. The response rate to ...