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C H A P T E R 1 4  Antineoplastic agents

TABLE 14.5

DRUGS IN FOCUS Hormones and hormone modulators (continued)

Drug name

Dosage/route

Usual indications

nilutamide (Anandron)

300 mg/day PO for 30 days, then 150 mg/day PO

With surgical castration for treatment of metastatic prostate cancer Actions: antioestrogenic drug, inhibits androgen uptake and binding on target cells Special considerations: may cause liver toxicity, and liver function test results should be monitored regularly; associated with interstitial pneumonitis—baseline and periodic chest radiographs should be obtained and drug discontinued at first sign of dyspnoea In combination therapy with surgery to treat breast cancer; treatment of advanced breast cancer in men and women; first drug approved for the prevention of breast cancer in women at high risk Actions: antioestrogen, competes with oestrogen for receptor sites in target tissues Special considerations: signs and symptoms of menopause are common effects; CNS depression, bone marrow depression and GI toxicity are also common; can change visual acuity and cause corneal opacities and retinopathy—pretherapy and periodic ophthalmic examinations are indicated Treatment of advanced breast cancer in women with oestrogen receptor–positive disease Actions: binds to oestrogen receptors and prevents growth of breast cancer cells Special considerations: signs and symptoms of menopause are common effects; CNS depression and GI toxicity are also common Treatment of advanced prostatic cancer Actions: analogue of luteinising hormone– releasing hormone; causes a decrease in follicle- stimulating hormone and luteinising hormone levels, leading to a suppression of testosterone production Special considerations: monitor prostate-specific antigen and testosterone levels regularly; sexual dysfunction, urinary tract symptoms, bone pain and hot flushes are common; schedule depot injections and mark calendar for person

20–40 mg/day PO

tamoxifen (Nolvadex, Tamosin)

toremifene (Fareston)

60 mg/day PO

triptorelin (Diphereline)

3.75-mg IM depot monthly or 11.25-mg IM depot every 3 months

Adverse effects Adverse effects frequently encountered with the use of these drugs involve the effects that are seen when oes­ trogen is blocked or inhibited. Menopause-associated effects include hot flushes, vaginal spotting, vaginal dryness, moodiness and depression. Other effects include bone marrow suppression and GI toxicity, including hepatic dysfunction. Hypercalcaemia is also encountered as the calcium is pulled out of the bones without oestrogen activity to promote calcium deposition. Many of these drugs increase the risk for cardiovascular disease because of their effects on the body.

Clinically important drug–drug interactions If hormones and hormone modulators are taken with oral anticoagulants, there is often an increased risk of bleeding. Care is also necessary when administering these agents with any drugs that might increase serum lipid levels. Prototype summary: Tamoxifen Indications: Treatment of metastatic breast cancer, reduction of risk of invasive breast cancer in women with ductal carcinoma in situ, reduction in occurrence of contralateral breast cancer in people