1. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc. Chapter 102 Anticancer Drugs II: Hormonal Agents, Biologic Response Modifiers, and Targeted Drugs

2. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.2 Hormonal Agents  Used primarily for breast cancer and prostate cancer  Mimic or block the actions of endogenous hormones  See Table 102-1

3. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.3 Biologic Response Modifiers  Enhance immune attack against cancer cells

4. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.4 Targeted Drugs  Bind with specific molecular targets on cancer cells to suppress tumor growth and promote cell death

5. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.8 Drugs for Prostate Cancer  Leuprolide (Lupron)  Triptorelin (Trelstar Depot, Trelstar LA)  Flutamide (Eulexin)  Bicalutamide (Casodex)  Nilutamide (Nilandron)  Diethylstilbestrol diphosphate (Stilphostrol)  Estramustine (Emcyt)

9. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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 Concurrent treatment with androgen receptor blocker can minimize these effects

11. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.11 Gonadotropin-Releasing Hormone Antagonists  Suppress production of androgens  Do not produce initial tumor flair  Abarelix  Degarelix

12. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.12 Androgen Receptor Blockers  Also known as antiandrogens  Indicated for advanced androgen-sensitive prostate cancer with castration  Flutamide  Bicalutamide  Nilutamide

13. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.13 Other Drugs for Prostate Cancer  Estrogens  Diethylstilbestrol diphosphate  Ketoconazole  Estramustine  Cytotoxic anticancer drugs

14. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.14 Breast Cancer  Most common cancer affecting women in the United States  Principal treatments  Surgery, radiation, cytotoxic drugs, and hormonal drugs

15. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.15 Drugs for Breast Cancer  Tamoxifen (Nolvadex)  Toremifene (Fareston)  Raloxifene (Evista)  Fulvestrant (Faslodex)  Anastrozole (Arimidex)  Letrozole (Femara)  Exemestane (Aromasin)  Trastuzumab (Herceptin)

16. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.17 Tamoxifen  Adverse effects  Hot flushes  Fluid retention  Vaginal discharge  Nausea and vomiting  Menstrual irregularities

18. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.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. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.19

20. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.20 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

21. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.21 EGFR-Tyrosine Kinase Inhibitors  Cetuximab (Erbitux)  Gefitinib (Iressa)  Erlotinib (Tarceva)

22. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.22 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

23. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.23 CD20-Directed Antibodies  Rituximab (Rituxan)  Ibritumomab tiuxetan linked with yttrium-90  Tositumomab and 131 I-tositumomab (iodine- 131) (BEXXAR)

24. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.24 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

25. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.25 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

26. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.26 Thalidomide (Thalomid)  Causes severe birth defects  Two approved indications  Erythema nodosum leprosum, a complication of leprosy  Multiple myeloma

27. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.27 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

28. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.28 Other Targeted Drugs  Sorafenib  Sunitinib  Gemtuzumab ozogamicin  Trastuzumab

29. Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.29 Other Noncytotoxic Anticancer Drugs  Retinoids  Alitretinoin  Bexarotene  Tretinoin  Arsenic trioxide  Denileukin diftitox  Bisphosphonates  Progestins