1 / 72

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.

hidalgo
Download Presentation

Chemotherapeutic Agents

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related