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Chemotherapeutic Agents

Chemotherapeutic Agents. Introduction. Classification of Drugs Cell-cycle specificity Mechanism of Action Indication Side effects . Antimetabolites. Cell-cycle specific Act in S-phase Inhibit enzyme production for DNA synthesis Lead to strand breaks or incomplete DNA strands.

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Chemotherapeutic Agents

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  1. Chemotherapeutic Agents

  2. Introduction • Classification of Drugs • Cell-cycle specificity • Mechanism of Action • Indication • Side effects

  3. Antimetabolites • Cell-cycle specific • Act in S-phase • Inhibit enzyme production for DNA synthesis • Lead to strand breaks or incomplete DNA strands

  4. Cytosine Arabinoside • Also called Ara-C or Cytarabine • Treatment for Leukemias and Lymphomas • Variety of dose schedules/routes • Myelosuppression, alopecia (dose dependant), N&V, mucositis, diarrhea, conjunctivitis, acral redness, liver and kidney dysfunction, neurologic dysfunction (high dose) • Non-vesicant

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

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

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

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

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

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

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

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

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

  14. Epipodophyllotoxins • Cell-cycle specific • Work in late G2 and S phase • Interfere with topoisomerase II enzyme • Stops cell replication in pre-mitotic phase

  15. Etoposide (VP-16) • Breast, testicular, SCLC, lymphomas • 100 mg/m2/day x 3 days q 28 days • Non-vesicant • Myelosuppression, N&V, alopecia, orthostatic hypotension • Rapid infusion causes hypotension-given over 45-60 min • Must be dilute or will precipitate

  16. Taxanes • Cell-cycle specific • Active in G2 and M phase • Stabilize the microtubule structure • Cells cannot divide

  17. Paclitaxel (Taxol) • Breast, ovarian, SCLC • Given IV over 24hrs, 3 hrs, or 1 hr • Myelosuppression, alopecia (severe), peripheral neuropathy, hypersensitivity rxns, myalgias, severe fatigue • Pre-meds: Dexamethasone 20 mg po 12 & 6 hrs prior, Pepcid or Tagamet, Benedryl plus anti-emetic • Need NON-PVC tubing with 0.2 micron in-line filter -- NON-PVC bag or bottle • IRRITANT • When given with other chemo drugs; give Taxol first

  18. Docetaxel (Taxotere) • Breast, NSCLC, head and neck, ovarian • 60 to 100 mg/m2 IV every 3 weeks • Myelosuppression, myalgias, hypersensitivity, peripheral neuropathy, alopecia (severe) • Pre-med: Dexamethasone 8 mg po bid starting 1 day prior and continuing 4 days after • Non-PVC tubing and bottle (no filter)

  19. Camptothecins • Cell-cycle specific • Act in S phase • Inhibit topoisomerase I • Causes double-strand DNA changes

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

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

  22. Miscellaneous • Cell-cycle specific • Work in a variety of ways • Inhibit Protein synthesis • Act in S phase • Inhibit RNA and DNA synthesis

  23. L-Asparginase (Elspar) • Leukemia • 1,000 - 6,000 IU/m2 IM • Hypersensitivity, anaphylaxis, hepatoxicity, N&V (slight), fever • ALWAYS give test dose prior to initial dose-test dose given intradermally • Also give test dose if pt has not had in more than 1 week • IM administration decreases hypersensitivity reactions

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

  25. Hydroxyurea (Hydrea) • Leukemias, Malignant melanoma, head and neck cancer, ovarian • 20 - 30 mg/kg PO q day • Myelosuppression, N&V (mild), mucositis, constipation or diarrhea • Dose is adjusted based on blood counts

  26. Alkylating Agents • Cell-cycle Nonspecific • Break DNA helix strand • Interfere with DNA replication

  27. Cisplatin • GU cancers, lung, head and neck, sarcomas, testicular, renal cell, esophageal • Doses no higher than 100 mg/m2 • Monitor K+, Mg+, Creatinine • Severe and prolonged N&V, nephrotoxocity, ototoxicity, myelosuppression, alopecia (mild) • Rigorous hydration needed to prevent renal toxicity • Irritant

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

  29. Oxaliplatin • Second line therapy for metatstatic colorectal cancer • Neuropathy starting within hours exacerbated by exposure to cold • Acute and chronic neuropathy • Neutropenia ( w/ 5-FU), Anemia Thrombocytopenia • Renally excreted • Irritant – use central line

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

  31. Ifosfamide (Ifex) • Lung, testicular, lymphomas, sarcomas • 1.2 gm/m2 IV days 1-5 q 3-4 wks • ALWAYS given with Mesna • Hermorrhagic cystitis, N&V, alopecia, myelosuppression, neurotoxicity • Mesna dose should be 20% of the Ifosfamide dose

  32. Mechlorethamine HCl(Nitrogen Mustard) • Leukemias, lymphomas • 6 mg/m2 IV on day 1 and day 8 q 4 weeks • Myelosuppression, N&V, chills, fever, pain at IV site • VESICANT • Flush with 125 - 150 cc NS • Stable for only 10 to 15 minutes; use immediately after mixing

  33. Dacarbazine (DTIC) • Lymphomas, Sarcoma, Melanoma • 75 - 1500 mg/m2 • Myelosuppression, N&V, alopecia, flu-like syndrome, renal and liver toxicity, diarrhea • VESICANT

  34. Thiotepa • Bladder, breast, ovarian, lymphomas • 0.3-0.4 mg/kg IV at 1 - 4 wk intervals; 0.6-0.8 mg/kg for bladder (intracavitary) administration • Myelosuppression, rash, fever, N&V • Monitor renal function if given IV

  35. Anti-tumor Antibiotics • Cell-cycle Nonspecific • Bind with DNA • Inhibit DNA and RNA synthesis

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

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

  38. Bleomycin (Blenoxane) • Lung, head and neck, cervical, GYN cancers, GU cancers, lymphomas • 10-20 units/m2 IV, IM, or SQ 1-2 times per week • Hypersensitivity, anaphylaxis, alopecia, photosensitivity, renal/hepatotoxicity, fever, chills, pulmonary fibrosis • Test dose of 1-2 units before 1st dose • Cumulative lifetime dose ~ 400 units due to risk for pulmonary fibrosis

  39. Mitomycin - C • GI tumors, breast, lung, head and neck, esophageal, bladder, multiple myeloma • 20 mg/m2 IV q 6-8 weeks • Myelosuppression, alopecia, mucositis, renal / pulmonary toxicity, fatigue • VESICANT • Nadir is 4 to 8 weeks • Brochospasm can occur when given simultaneously or after Vinca alkaloid • Extravasation can occur distant from IV site

  40. Mitoxantrone (Novantrone) • Breast, lymphomas, leukemia (ALL) • 12 - 14 mg/m2 every 21 days • Myelosuppression, alopecia, cardiotoxicity • Urine blue-green with 1st post void • VESICANT

  41. Hormonal Therapy • Cell-cycle Nonspecific • Interfere with hormone receptors • Interfere with protein synthesis in all phases of cell cycle

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

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

  44. Progestins • Depo-Provera ; Megace • Breast, renal cell • Depo-Provera: 400-1,000 mg IM q wk; Megace: 40 - 320 mg/day in divided doses PO • Fluid retention, headache, vaginal bleeding/spotting, increased appetite, thrombophlebitis • Megace used as appetite stimulant • Depo-provera used to prevent menses in thrombocytopenic patients

  45. Leuprolide (Lupron) • Prostate, breast cancer • Dose varies with protocol • Gynecomastia, hot flashes, N&V, headache, bone pain • Symptoms may worsen in first few weeks of therapy.

  46. Goserelin acetate (Zoladex) • Prostate, breast cancer • Dose varies with protocol • Hot flashes, gynecomastia, N&V • Given as depot injection SQ into abdomen (with 14-16 gauge needle) once a month or every 3 months

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

  48. Carmustine (BCNU) • Lymphomas, CNS tumors, multiple myeloma, melanoma, BMT • 75-100 mg/m2 IV x 2 days or 200 mg/m2 IV single dose q 6-8 wks • N&V, myelosuppression, renal/liver toxicity, pulmonary fibrosis • Nadir: 4-6 weeks • Crosses blood/brain barrier • Rapid infusion causes facial flushing and hypotension

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

  50. Antibodies/Antigens Antibodies Antigens CELL

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