Chemotherapy III Flashcards
Topoisomerase II Inhibitors: Intercalators
Daunomycin
Doxorubicin
Mitoxantrone
Dactinomycin
Topoisomerase II Inhibitors:
Non-intercalators
Etoposide
Topoisomerase I Inhibitors
Topotecan
Irinotecan
Which drugs are cross resistant due to MDR?
Non-intercalating topo II inhibitors Intercalating topo II inhibitors Tubulin Inhibitors (alkaloids)
What is one way to reverse MDR resistance?
Give drugs as continuous infusions > downregulate the P glycoprotein
What is the P glycoprotein?
Membrane bound efflux pump
Which drugs can block the efflux pump and reverse resistance?
Quinine
Verapamil
Cyclosporine
Which anticancer drugs are MDR cells resistant to?
Vinca alkaloids (Vinblastine, Vincristine)
Anthracyclines (Daunorubicin, doxorubicin, mitroxantrone)
Epipodophyllotoxins (Etoposide, Teniposide)
Mitomycin C
Actinomycin D
Taxol
Topotecan
Doxorubicin MOA
Cell cycle non-specific
Intercalates into DNA and inhibits topo II producing double stranded DNA breaks
When should you dose reduce doxorubicin?
Jaundice (excreted in bile)
Doxorubicin SE
Nausea, vomiting, hair loss, stomatitis
MYELOSUPPRESSION = d-l
What can the cumulative toxicity of doxorubicin cause? What is the max life time dose?
Cardiomyopathy
400 mg/M^2
Schedule dependent
What should you obtain before administering doxorubicin?
EJECTION FRACTION
How can you reduce the cardiac toxicity of Doxorubicin?
Give longer infusion times (96 hour)
Pretreat with an iron chelator (dexrazoxane)
Irinotecan MOA
Topoisomerase I inhibitor
Requires bioactivation
When should you dose reduce Irinotecan?
Jaundice
Irinotecan SE
Early diarrhea (during infusion or first 24 hours)
Late diarrhea (7-10 days after)
How can you treat the early and late diarrhea of Irinotecan?
Early: treat with atropine (cholinergic)
Late: treat with imodium, hydration
What genetic mutation/Syndrome will cause increase myelosuppression and diarrhea with Irinotecan?
UGT1A1*28
(decreases glucoronidation)
Gilbert’s Syndrome
Irinotecan Indication
Colon cancer
Bleomycin MOA
Cell cycle specific
Free radical damage to DNA
When should you dose reduce bleomycin?
Renal insufficiency
Which organs can inactivate Bleomycin?
Which organs cannot?
Liver and kidney
Lungs and Skin
Bleomycin SE
Skin hyperpigmentation
PULMONARY TOXICITY = d-l
(cumulative toxicity)
Anaphylactoid reactions
What should you monitor in a patient taking Bleomycin?
Pulmonary function (Diffusion capacity of carbon monoxide-DLCO)
Obtain baseline pulm function tests prior to administration
What should you avoid administering in a patient taking Bleomycin?
High oxygen concentrations
Bleomycin Indication
Testicular Cancer
Hormone dependent cancers
Breast cancer
Prostate cancer
Prednisone Indication
Myeloproliferative or Lymphoproliferative Disorders:
Multipl Myeloma, Hodgkin’s disease, non-hodgkin’s lymphoma, leukemia (some)
Prednisone SE
Weight gain, HTN, edema, carb intolerance, suppression of pituitary-adrenal axis, weakness, euphoria, increased appetite
Dexamethasone Indications
Chemotherapy related nausea and vomiting (use with 5-HT3 inhibitors)
Cerebral edema, spinal cord edema due to spinal cord compression
Tamoxifen
Oral selective estrogen receptor modulator (SERM)
Tamoxifen MOA
Agonist-antagonist with respect to estrogen receptor (antagonist in cancer cell)
Tamoxifen SE
Hot flashes
Thrombosis
Endometrial cancer
Decreases rate of bone loss
Tamoxifen Indication
Prevents breast cancer in high risk women who take for 5 years
Aromatase Inhibitors MOA
Rapidly decrease estrogen levels
Aromatase Inhibitors Indication
Estrogen receptor positive breast cancers
Aromatase Inhibitors SE
Arthralgias, bone pain, bone loss, osteoporosis, hot flashes
Aromatase Inhibitors
Anastrozole, Letrozole, Exemestane
Goal of Prostate Cancer treatment
decrease testosterone production > Androgen deprivation therapy
Flutamide/ Bicalcutamide MOA
Inhibit cancer cell uptake of testoterone
Leuprolide acetate MOA
Decrease levels of androgens by decreasing FSH and LH by using a gonadotropin releasing hormone agonist
What can you pretreat with to avoid the tumor flare of Leuprolide acetate?
Flutamide
Bicualutamide
Side effects of Androgen Deprivation Therapy?
Weakness Decreased libido Erectile dysfunction Loss of muscle mass Gynecomastia Change in body fat distribution