pharm onc

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dtminhthu
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71811
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pharm onc
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2011-03-20 21:06:58
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pharm onc
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pharm onc
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  1. Mucositis common with...
    5-FU, Busulfan, alkylating agents, radiation
  2. prevents nausea/vomiting at level of CTZ
    5HT3 Antag (Ondansetron), NK1 Antagonist (Aprepitant), Phenothiazines
  3. Prochlorperazine
    • anti D2 receptor. Antiemetic and migraine treatment.
    • Adverse: dystonias and orthostatic hypotension
  4. Cyclophosphamide pharmacokinetics
    activated via cytochrome P450. Inactivated by aldehyde dehydrogenase
  5. MAO inhibitor and nonclassical alkylating agent
    Procarbazine
  6. Nephrotoxicity, ototoxicity, N/V, peripheral neuropathies, myelosuppression
    Platinums.
  7. Pure estrogen receptor antagonist. Inhibits dimerization of the occupied receptor; thus there is no binding to the DNA. Effective in resistant tamoxifen patients. Monthly injection
    Fulvestrant
  8. Treatment of anti-estrogen resistant advanced breast cancer or as first line adjuvant in postmenopausal women.
    Do not suppress mineralocorticoid or glucocorticoid production
    • Non steroidal aromatase inhibitors Anastrozole and Letrozole
    • Exemestane - Steroidal (irreversible inhibitor of aromatase)
  9. LHRH (Leutinizing Hormone Releasing Hormone) agonist
    Leuprolide, Goserelin. Inhibits synthesis of sex steroids in both men and women. Suppression of androgen synthesis. Reduction of PSA. Used mostly for prostate cancer; sometimes in combination with an antiandrogen (flutamide)
  10. Nonsteroidal antiandrogen which blocks androgen at receptor site. Used in combination at the beginning of therapy with LHRH analogue for prostate cancer to prevent tumor flare
    Flutamide
  11. Nonsteroidal synthetic estrogen to suppress androgen synthesis
    Diethylstilbestrol
  12. Most widely used agent for Colorectal cancer; alsobreast, bladder, esophagus. Can lead to mucositis and myelosuppression
    5-FU
  13. Complex, poor oral bioavailability, thus only given I.V. Undergoes reduction by a dehydrogenase enzyme. Metabolism follows zero-order kinetics at high doses
    5-FU
  14. Vinca alkaloid MOA
    • Binds to the microtubular protein tubulin in a dimeric form
    • The drug-tubulin complex adds to the forming end of the microtubules to terminate assembly
    • Depolymerization of the microtubules occurs
  15. Myelosuppression
    Peripheral neuropathy, constipation, ileus, Alopecia
    SIADH, Vesicant
    Fatal if given intrathecally (Never!)
    Liver Metabolism. Reduce dose if Total Bili > 3mg/dl
    Adverse effects of Vinca alkaloids
  16. Myelosuppression, Peripheral Neuropathy
    Hypersensitivity reactions
    Capillary leak
    Edema
    Toxicities of Taxanes
  17. Taxane therapeutic uses
    • Paclitaxel- ovarian (with cisplatin) and advanced breast cancer, lung cancer, and Kaposi’s sarcoma
    • Docetaxel- advanced breast cancer, head and neck cancer, gastric cancer, bladder cancer, platinum refractory ovarian cancer.
  18. High-affinity binding to DNA through intercalation, resulting in blockade of DNA and RNA synthesis
    DNA strand scission via effects on Topoisomerase II
    Binding to membranes altering fluidity
    Generation of oxygen radicals
    Anthracycline MOA
  19. Binds to DNA through an antibiotic-Mg2+ complex
    This interaction interrupts DNA-directed RNA synthesis
    Plicamycin
  20. Adverse effects: liver toxicity, bleeding disorder, hypocalcemia
    Use: testicular cancer, hypercalcemia
    Plicamycin
  21. Bioreductive alkylating agent that undergoes metabolic reductive activation through an enzyme-mediated reduction to generate an alkylating agent that cross-links DNA.
    Mitomycin
  22. Adverse Effect: renal toxicity, lung fibrosis, bone marrow toxicity, hemolytic anemia.
    Use: bladder tumors, gastric adenocarcinoma, hypoxic tumor.
    Mitomycin
  23. Binds to double stranded DNA through intercalation between adjacent guanine-cytosine base pairs
    Inhibits all forms of DNA-dependent RNA synthesis
    Inhibits DNA transcription
    Hepatic metabolism
    Actinomycin
  24. Adverse effects: oral ulcers, sun sensitivity, immunosuppression
    Use: Wilm’s tumor
    Actinomycin
  25. Acts through binding to DNA, which results in single and double strand breaks following free radical formation and inhibition of DNA synthesis
    accumulation of cells in G2
    Bleomycin
  26. Lethal anaphylactoid reactions
    Skin discoloration
    Pulmonary fibrosis (those over 70 years old or have undergone chest irradiation, or underlying pulmonary disease).
    Raynaud’s syndrome, Alopecia, Mucositis
    Bleomycin adverse effects
  27. Testicular cancer, Squamous cell carcinomas of the head and neck, cervix, skin, penis, and rectum
    Lymphomas
    Intracavitary therapy in ovarian and breast cancers
    Bleomycin uses
  28. Antibodies for CD20
    • Rituximab
    • Ibritumomab
    • Tositumomab
  29. Antibodies for CD33
    Gemtuzumab-Ozogamicin
  30. Antibodies for CD52 (found on all mature lymphocytes)
    Alemtuzumab
  31. Antibody for VEGF
    Bevacizumab
  32. Antibody for EGFR
    Cetuximab
  33. Non-Hodgkin's lymphoma treatment
    • RCHOP.
    • Rituximab

    • Cyclophosphamide

    • Hydoxydaunorubicin (doxorubicin)

    • Oncovin (vincristine)

    • Prednisolone
  34. FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
    Rituximab
  35. derivative of Rituximab which is radiolabeled with Ytrium
    For CD20. Ibritumomab
  36. I-131 radiolabeled Rituximab
    For CD20. Tositumomab
  37. Advantages: Better efficacy, fewer doses.
    Disadvantages: Toxicity (Neutropenia, thrombocytopenia, infection (30%); More labor
    Radiolabeled Rituximabs: Ibritumomab and Tositumomab
  38. 1,000 x as toxic to CD33 cells as is doxorubicin
    Calicheamicin
  39. Chronic Lymphocytic Leukemia (CLL), T-Cell Lymphoma and Cutaneous T-Cell Lymphoma.
    Toxicity may include Infusion Related Events, which may include respiratory or cardiac death.
    Aims at CD52. Alemtuzumab
  40. Bevacizumab therapeutic use
    VEGF Ab. colon cancer, lung cancer, breast cancer
  41. GI perforation, intra-abdominal abscesses.
    Wound dehiscence, a spontaneous separation of wound or surgical repair.
    Hypertensive crisis
    Nephrotic syndrome
    Congestive heart failure, Myocardial Infarction
    Weakness, Leukopenia
    Bevacizumab toxicity
  42. Chimeric (mouse/human) monoclonal antibody. EGFR inhibitor. IV infusion for metastatic colon cancer, head and neck cancer
    Cetuximab
  43. Severe acne rash that is reversible. Infusion rxn that may be mediated by H1 histamine receptor. Toxicity can be prevented via diphenhydramine
    Cetuximab
  44. Cardiac Toxicity, Increased risk for cardiac death.
    Contraindicated with Anthracyclines.
    Cost: Approx. $70,000-$100,000 per year.
    Trastuzumab
  45. highly protein bound
    CYP3A4 substrate
    Half-life (t1/2) = 12-36 hours
    Small molecule tyrosine kinase inhibitors. -nibs
  46. Myelosuppression
    Fluid retention & edema (dose-related)
    Pleural effusions, ascites, pulmonary edema, rapid weight gain, CHF (rare)
    Nausea, diarrhea, abdominal pain
    Musculoskeletal pain, myalgias
    Rash, Hepatotoxicity (can be severe)
    Adverse effects of Imatinib
  47. Prodrug that can be used along w/ Lapatinib for Her2/neu breast cancer. Converted to 5-FU in tumor
    capecitabine
  48. Inhibits VEGF
    Labeled indications: Advanced renal cell carcinoma, Unresectable hepatocellular carcinoma
    Sorafenib
  49. Inihibts VEGF and c-kit
    Labeled indications: GI stromal tumor w/ failure or intolerance to imatinib
    Advanced renal cell carcinoma
    Sunitinib
  50. Myelosuppression, GI effects, hand foot syndrome, hypertension, bleeding, hair color changes
    sorafenib
  51. Myelosuppression, GI effects, hand foot syndrome, bleeding, incr QT, hypothyroidism, skin discoloration, and venous thromboembolic events
    sunitinib
  52. Drugs that lead to hand foot syndrome
    • 5-FU, capecitabine, cytarabine, doxorubicin
    • TKIs: sorafenib and sunitinib.
  53. Inhibits EGFR (Her2/neu)
    Lapatinib, Gefitinib, Erlotinib
  54. Approved world-wide for non-small cell lung carcinoma (NSCLC).
    EGF tyrosine kinase receptor (EGFR) inhibitor
    Side effects: Acne, GI, asthenia.
    Gefitinib
  55. INHIBITS HER-1 (EGFR)
    Non-small cell lung cancer (NSCLC) – locally advanced or metastatic in patients who have failed at least one prior chemotherapy regimen
    Pancreatic cancer – locally advanced, unresectable or metastatic in combination with gemcitabine
    Erlotinib
  56. Reversible inhibitor of 26S Proteosome
    Increases cellular protein, including tumor suppressors. May prevent degradation of pro-apoptotic molecules, allowing continued programmed cell death in neoplastic cells
    Bortezomib
  57. GI upset and asthenia, a state of general weakness.
    Peripheral neuropathy with pain
    Shingles, Neutropenia, Thrombocytopenia
    Bortezomib
  58. analog of cytidine, and is incorporated into DNA during replication and RNA during transcription.
    Azacytidine inhibits methyltransferase and causes demethylation of its segment of DNA and RNA.
    Azacytidine
  59. Indicated for myelodysplastic syndrome of neutropenia, thrombocytopenia, anemia
    Azacytidine
  60. GI symptoms, Neutropenia, Thrombocytopenia, Liver dysfunction
    side effects of Azacytidine

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