Nursing Pharmacology: Anticancer Agents: Hormones
Breast and prostatic cancer: palliation with sex hormone therapy
Adrenal corticosteroid treatment-- useful in:
Acute leukemia
Myeloma
Lymphomas
Other hematologic cancers
Pharmacological effects:
Steroid hormones bind to steroid receptors:
Efficacy of steroid treatment depends on specific receptor presence on malignant cell surface.
Clinical Use: Treatment of:
Female and male breast cancer
Prostatic cancer
Endometrial cancer of uterus
Adverse Effects:
Fluid retention (secondary to Na-retaining properties)
Androgens-masculinization (long-term use)
Estrogens-feminization (long-term use)
Adrenocortical steroids:
Hypertension
Diabetes
Enhanced susceptibility to infection
Cushingoid appearance
Estrogen and Androgen Inhibitors: (Tamoxifen and Flutamide)
Tamoxifen: Breast cancer treatment
Oral administration.
Activity against progesterone-resistant endometrial neoplasm
Chemopreventive:women whho are at high-risk for breast cancer
Mechanism of Action:
Competitive partial agonist-inhibitor of estrogen
Binds to estrogen-sensitive tissues (receptors present)
Best antiestrogen effect requires minimal endogenous estrogen presence (estradiol has a much higher affinity for the estrogen receptor than tamoxifen's affinity for the estrogen receptor)
Suppresses serum levels of insulin-like growth factor-1; and up-regulates local TGF-beta production. These properties may explain tamoxifen antitumor activity in melanoma and ovarian cancer.
Adverse Effects:
Generally mild
Most frequent: hot flashes
Occasionally: fluid retention, nausea
Clinical Use:
Advanced breast cancer
Most likely to be effective if:
Lack endogenous estrogens (oophorectomy; postmenopausal)
Presence of cytoplasmic estrogen receptor;presence of cytoplasmic progesterone receptorColeman
Prolongs survival (surgical adjuvant therapy) in postmenopausal women with estrogen receptor-positive breast cancer.
Flutamide (Eulexin): prostatic cancer
Antagonizes remaining androgenic effects after orchiectomy or leuprolide treatment
Gonadotropin-Releasing Hormone Agonists (Leuprolide and Goserelin (Zoladex))
Leuprolide and goserelin: synthetic peptide analogues of gonadotropin-releasing hormone (GnRH, LHRH)
Mechanism of Action: Analogues more potent -- behave as GnRH agonists.
Pituitary effects: when given continuously -- initial stimulation then inhibition of follicle-stimulating hormone and leutinizing hormone.
Causes reduced testicular androgen synthesis, the reason why these agents are effective in treating metastatic prostate carcinoma
Clinical Use: treating metastatic prostate carcinoma
Comparing leuprolide with diethylstilbestrol (DES):
Similar suppression of androgens synthesis and serum prostatic acid phosphatase (an index of metastatic tumor load)
Adverse Effects: Leuprolide less frequently causes:
Nausea
Vomiting
Edema
Thromboembolism
Painful gynecomastia
Leuprolide and goserelin: medication more costly, the more cost-effective given reduced frequency of complications.
Aromatase Inhibitors (Aminoglutethimide and Anastrozole (Arimidex))
Mechanisms of action: Reduction in estrogen concentration
Aminoglutethimide: inhibitor of adrenal steroid synthesis ( blocks conversion of cholesterol to pregnenolone (first-step))
Aminoglutethimide inhibits extra-adrenal estradiol and estrone synthesis.
Aminoglutethimide inhibits an aromatase enzyme (catalyzes conversion of androstenedione to estrone)
This conversion may occur in fat.
Clinical Use:
Metastatic breast cancer (tumors contain estrogen or progesterone receptors)
Aminoglutethimide is administered with adrenalreplacement doses of hydrocortisone to ensure avoidance of adrenal insufficiency.
Hydrocortisone is used in preference to dexamethasone, because dexamethasone increases the degradation of aminoglutethimide.
Aminoglutethimide in combination with hydrocortisone: Second-Line Therapy for women treated with tamoxifen (aminoglutethimide causes more adverse side effects than tamoxifen)
Anastrozole (Arimidex): new, selective, nonsteroidal aromatase inhibitor.
Appears to have no effect on glucocorticoid or mineralocorticoid synthesis
Clinical Use:
Treatment of advanced estrogen-or progesterone-receptor positive non--tamoxifen responsive breast cancer
Salmon, S. E. and Sartorelli, A. C. Cancer Chemotherapy, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 881-911.