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Chapter 102

Chapter 102. Anticancer Drugs II: Hormonal Agents, Biologic Response Modifiers, and Targeted Drugs. Hormonal Agents. Used primarily for breast cancer and prostate cancer Mimic or block the actions of endogenous hormones See Table 102-1. Biologic Response Modifiers.

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Chapter 102

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  1. Chapter 102 Anticancer Drugs II: Hormonal Agents, Biologic Response Modifiers, and Targeted Drugs

  2. Hormonal Agents • Used primarily for breast cancer and prostate cancer • Mimic or block the actions of endogenous hormones • See Table 102-1

  3. Biologic Response Modifiers • Enhance immune attack against cancer cells

  4. Targeted Drugs • Bind with specific molecular targets on cancer cells to suppress tumor growth and promote cell death

  5. Glucocorticoids • High doses required for cancer patients • Used in combination with other agents to treat lymphoid tissue cancers (directly toxic) • Acute and chronic lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphomas, and multiple myeloma • Multiple serious side effects with high doses

  6. Glucocorticoids • Also used to manage complications of cancer and cancer therapy • Suppression of chemo-induced nausea and vomiting • Reduction of cerebral edema • Reduction of pain • Suppression of hypercalcemia in steroid-responsive tumors • Can improve appetite and promote weight gain

  7. Prostate Cancer • Most common cause of cancer among men in United States • Standard treatment of advanced prostate cancer • Androgen deprivation • Slows disease progression and increases comfort • Lower testosterone production • Block testosterone receptors with drugs

  8. Drugs for Prostate Cancer • Leuprolide (Lupron) • Triptorelin (Trelstar Depot, Trelstar LA) • Flutamide (Eulexin) • Bicalutamide (Casodex) • Nilutamide (Nilandron) • Diethylstilbestrol diphosphate (Stilphostrol) • Estramustine (Emcyt)

  9. Gonadotropin-Releasing Hormone Agonists • GmRH • Suppress production of androgens by the testes • GmRH drugs for prostate cancer • Leuprolide, triptorelin, goserelin • Cotreatment with an androgen receptor blocker

  10. Gonadotropin-Releasing Hormone Agonists • Adverse effects • Generally well tolerated • Hot flushes • Testosterone loss may aggravate bone pain and urinary obstruction • Concurrent treatment with androgen receptor blocker can minimize these effects

  11. Gonadotropin-Releasing Hormone Antagonists • Suppress production of androgens • Do not produce initial tumor flair • Abarelix • Degarelix

  12. Androgen Receptor Blockers • Also known as antiandrogens • Indicated for advanced androgen-sensitive prostate cancer with castration • Flutamide • Bicalutamide • Nilutamide

  13. Other Drugs for Prostate Cancer • Estrogens • Diethylstilbestrol diphosphate • Ketoconazole • Estramustine • Cytotoxic anticancer drugs

  14. Breast Cancer • Most common cancer affecting women in the United States • Principal treatments • Surgery, radiation, cytotoxic drugs, and hormonal drugs

  15. Drugs for Breast Cancer • Tamoxifen (Nolvadex) • Toremifene (Fareston) • Raloxifene (Evista) • Fulvestrant (Faslodex) • Anastrozole (Arimidex) • Letrozole (Femara) • Exemestane (Aromasin) • Trastuzumab (Herceptin)

  16. Tamoxifen • Used for established disease and for decreasing occurrence in high-risk patients • Adjuvant therapy after surgery • Treatment of metastatic disease • Blocks and activates receptors in certain tissues

  17. Tamoxifen • Adverse effects • Hot flushes • Fluid retention • Vaginal discharge • Nausea and vomiting • Menstrual irregularities

  18. Biologic Response Modifiers: Immunostimulants • Drugs that alter the host responses to cancer • Interferon alfa-2a and interferon alfa-2b • Aldesleukin (interleukin-2) (Proleukin) • BCG vaccine (TheraCys, TICE BCG, Pacis)

  19. Targeted Drugs • Designed to bind with specific molecules that drive tumor growth • Many are antibodies that bind with specific antigens on tumor cells • See Table 102-4

  20. EGFR-Tyrosine Kinase Inhibitors • Cetuximab (Erbitux) • Gefitinib (Iressa) • Erlotinib (Tarceva)

  21. BCR-ABL Tyrosine Kinase Inhibitors • Preferred drugs for chronic myeloid leukemia (CML) • Imatinib (Gleevec) • Considered the model of a successful targeted anticancer drug • Highly effective • Well tolerated

  22. CD20-Directed Antibodies • Rituximab (Rituxan) • Ibritumomab tiuxetan linked with yttrium-90 • Tositumomab and 131I-tositumomab (iodine-131) (BEXXAR)

  23. Angiogenesis Inhibitors • Suppress formation of new blood vessels • Deprive solid tumors of blood supply needed for growth • Bevacizumab (Avastin) • Only one approved for treating cancer • Thalidomide (Thalomid) • See Box 102-1

  24. Bevacizumab • Metastatic colorectal cancer • Can delay tumor progression and prolong life • Adverse effects: GI perforation, hemorrhage, disruption of wound healing, nephrotic syndrome, hypertensive crisis, and thromboembolism

  25. Thalidomide (Thalomid) • Causes severe birth defects • Two approved indications • Erythema nodosum leprosum, a complication of leprosy • Multiple myeloma

  26. Proteasome Inhibitors • Disrupts various aspects of cell physiology by causing proteins to accumulate • Bortezomib (Velcade) • Approved for multiple myeloma • Adverse effects • Weakness, nausea, diarrhea, thrombocytopenia, anemia, neutropenia, constipation, anorexia

  27. Other Targeted Drugs • Sorafenib • Sunitinib • Gemtuzumab ozogamicin • Trastuzumab

  28. Other Noncytotoxic Anticancer Drugs • Retinoids • Alitretinoin • Bexarotene • Tretinoin • Arsenic trioxide • Denileukin diftitox • Bisphosphonates • Progestins

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