1. IMMUNOMODULA TING AGENTS. Chemotherapeutic Agents

6. 5-Flurouracil (5-FU) n Treatment for GI, breast, and ovarian cancers n Variety of dose schedules n Mucositis and Diarrhea, mild alopecia, photosensitivity, darkening and sclerosing of veins, skin changes, mild to no N&V n Potentiates radiation therapy--may be given concurrently n Leucovorin increases toxicity n Non-vesicant

8. Methotrexate n Treatment for lymphomas, leukemias, ovarian, breast, lung, testicular, cervical, and CNS mets n May be given for non-cancer dx n Variety of dose schedules/routes n Mucositis and diarrhea, N&V, alopecia, Myelosuppression, photosensitivity, renal toxicity n Given with Leucovorin (rescue) n Non-vesicant

10. Fludarabine n Treatment for CLL n 25 mg/m2 IV for 5 days n Given as 30 minute infusion n Myelosuppression, nausea, slight alopecia, rash, diarrhea

11. Capecitabine (Xeloda) n Treatment for breast cancer n Pro-drug -- turns to 5-FU in body n 2,500 mg/m2 orally for 14 days on and 7 days off n Take with food n Diarrhea, Mucositis, numbness, tingling, itching of hands and feet (hand and foot syndrome)

12. Gemcitabine (Gemzar) n Treatment for pancreatic, lung, and many other cancers n 1000mg/m2 IV every week up to 7 weeks in a row n Given as a 30 minute infusion-- longer infusions increase toxicity n Myelosuppression, N&V, fatigue, increased liver enyzmes, alopecia n Non-vesicant

13. Vinca Alkaloids n Cell-cycle Specific n Act in late G2 phase, M phase, and S phase n Block DNA and RNA production, prevent cell division, inhibit microtubule formation

15. Vinorelbine (Navelbine) n Treatment for lung, breast cancer n 30 mg/m2 IV weekly n VESICANT n Given IV push over 6 -10 min through side port of fast running IV (furthest from IV site), f/b 100 cc flush n Myelosuppression, Peripheral neuropathy, N&V, mild alopecia

16. Vincristine (Oncovin) n Treatment for leukemias, breast, lymphoma, SCLC, sarcoma n 1.4mg/m2 IV weekly n DOSE NOT TO EXCEED 2 mg n VESICANT n Peripheral neuropathy, constipation, paralytic ileus, jaw pain n Neuropathy is cumulative n FATAL IF GIVEN INTRATHECALLY

17. Vinblastine (Velban) n Testicular, Head and neck cancer, Hodgkin’s disease, Kaposi’s sarcoma n 4 - 18 mg/m2 IV weekly n VESICANT n Peripheral neuropathy, constipation, myelosuppression, mild alopecia, jaw pain n Less neuropathy than vincristine

18. Topotecan (Hycamtin) n Ovarian, salvage therapy n 1.5 mg/m2 IV daily x 5 days q 3 weeks n Myelosuppression, diarrhea, mild alopecia

19. Irinotecan (Camptosar) n Metastatic colon and rectum n 125 mg/m2 IV weekly x 4 weeks n Diarrhea (severe), Myelosuppression, alopecia n Diarrhea MUST be treated -- patients need to go home with antidiarrheal and know how to use it

20. Pegaspargase (Oncaspar) n Leukemics who are sensitive to Elspar n 2,500 IU/m2 IM every 14 days n Hepatotoxicity, coagulopathy, may have some hypersensitivity rxns n Less hypersensitivity than Elspar - may not need test dose n VERY expensive

22. Carboplatin n Ovarian, testicular, head and neck, lung, cervical n Varied dosing; sometimes ordered as AUC (area under the curve) n Thrombocytopenia, N&V, hyper- sensitivity, myelosuppression, renal/hepatic toxicity n No need for rigorous pre- or post- hydration

23. Cyclophosphamide (Cytoxan) n Breast, lung, prostate, ovary, leukemias, lymphomas, Multiple Myeloma, head and neck n Varied dosing schedule/route n Hemorrhagic cystitis, myelosuppression, N&V, alopecia, SIADH, nasal burning n Patient should drink 8 -10 glasses of water per day

25. Doxorubicin (Adriamycin) n Breast, ovary, prostate, stomach, lung, liver, head and neck, multiple myeloma, lymphomas, leukemias n 40-75 mg/m2 q 3 weeks n Myelosuppression, N&V, alopecia, mucositis, cardiotoxicity, radiation recall, photosensitivity, red urine n VESICANT n May cause flare reaction n MUGA / Echocardiogram before dosing n Lifetime cumulative dose 450-550mg/m2

26. Liposomal Doxorubicin (Doxil) n Refractory ovarian, Kaposi’s sarcoma n 50 mg/m2 IV q 4 weeks n Myelosuppression, palmar-plantar erythrodysesthesia, cardiotoxicity, mucositis, N&V, rash, alopecia n Start infusion at 1 mg/min and check for flushing, SOB, facial swelling, hypotension. If none, give over 30-60 minutes n Irritant; not vesicant

27. Glucocorticoids n Prednisone, dexamethasone, etc. n Breast, lymphomas, multiple myeloma, leukemias, CNS tumors or mets n Various dosing schedules n Fluid retention, hyperglycemia, GI irritation, masks infections, mood swings, moon face, osteoporosis, perineal burning with rapid infusion

28. Tamoxifen n ER+, postmenopausal breast cancer n 10 mg tab po BID n Vaginal bleeding/discharge, hot flashes, N&V, risk of uterine cancer n Usually given for 5 years-no evidence for continued use n Given as preventative in high-risk women

30. Nitrosoureas n Cell-cycle Nonspecific n Break DNA helix n Interfere with DNA replication n Cross blood-brain barrier

31. Monoclonal Antibodies n Cell-cycle Nonspecific n Uses antibody to target specific cells n Bind to markers on cell surface n Induce cell death (apoptosis) n Initiate complement system which results in cell phagocytosis

32. Antibodies/Antigens CELL Antigens Antibodies

33. How Antibodies Work

34. How MoAbs Are Produced

35. Various Types of MoAbs Adapted from LoBuglio A, et al. Crit Rev Oncol Hematol. 1992;13:273.

36. Rituximab (Rituxan) n Leukemias, lymphomas, ITP, Waldenstrom’s macroglobulinemia n 375mg/m2 IV; schedule varies n Start at 50 mg/hr; increase gradually if no reaction. n Infusion-related side effects; fever with rigors, hypotension, allergic reactions, N&V, pain n Pre-med: Tylenol and Benedryl

38. Ibritumomab (Zevalin) n Anti-CD 20 antibody bound to Tiuxetan—which binds to Yittrium 90 or Indium 111 n Dose = 0.4 mCi/kg n Given in Nuclear Medicine n Cannot be given if platelets < 100,000 u Dose reductions based on platelet count