Antineoplastics Exam 4 Flashcards
Vincristine (Oncovin)
Class: Vinca Alkaloids
MOA: Bind to tubulin at the forming end of microtubules and terminate spindle assembly.
Resistance: Efflux via P-glycoprotein (MDR), Changes in target proteins (mutated tubulin prevents binding)
Therapeutic Uses: Routinely used in combination therapy due to distinct MOA and toxicities.
Regimens (Oncovin): MOPP (Hodgkin’s), CHOP
Toxicity: Bone marrow suppression (less than vinBlastine); CNS neurotoxicity (vinCristine), N/V (more w/ vinblastine), vesicant
Neurotoxicity –> prominent due to microtubule needs for axonal transport. Common symptoms = motor: loss of reflexes; autonomic: constipation, paralytic ileus, orthrostatic hypotension; sensory: paresthesias ‘pins and needles”
Depression of DTR occurs within 2-3 weeks in 100% of patients –> used as indication of sufficient dose.
Severe paresthesias are used as an indication to decrease the dose.
Vinblastine
Class: Vinca Alkaloids
MOA: Bind to tubulin at the forming end of microtubules and terminate spindle assembly.
Resistance: Efflux via P-glycoprotein (MDR), Changes in target proteins (mutated tubulin prevents binding)
Therapeutic Uses: Routinely used in combination therapy due to distinct MOA and toxicities.
Regimens: ABVD (Hodgkin’s) and PVB for testicular cancer
Toxicity: Bone marrow suppression (less than vinBlastine); CNS neurotoxicity (vinCristine), N/V (more w/ vinblastine), vesicant
Neurotoxicity –> prominent due to microtubule needs for axonal transport. Common symptoms = motor: loss of reflexes; autonomic: constipation, paralytic ileus, orthrostatic hypotension; sensory: paresthesias ‘pins and needles”
Depression of DTR occurs within 2-3 weeks in 100% of patients –> used as indication of sufficient dose.
Severe paresthesias are used as an indication to decrease the dose.
Taxanes (Capazitaxel, Docataxel, and Paclitaxel)
MOA: Bind to tubulin and enhance and stabilize spindle assembly.
Resistance: Decreased Accumulation via increased P-glycoprotein expression (MDR)
PK: Extensive CYP450 metabolism
Toxicities: Bone marrow suppression, hypersensitivity/ allergic reactions peripheral neuropathy, N/V, hypotension/arrhythmias
Vinorelbine
Class: Vinka Alkaloids
MOA: Bind to tubulin at the forming end of microtubules and terminate spindle assembly.
No notes about this drug made by Fitz –> treat like vincristine/vinblastine
Ixabepilone
Class: Epilone
MOA: Binds to tubulin and enhance and stabilize spindle assembly (similar to paclitaxel).
Use: Third line for Breast Cancer with Capecitabine
PK: Metabolized in the liver
Toxicities: Bone marrow suppression, peripheral neuropathy, and cardiac arrhthmias, and hypersensitivity
Resistance: P-glycoprotein efflux (MDR)
Prednisone and Dexamethasone
Corticosteroids
MOA (immune system): Interfere w/ concentration, distribution, and function of leukocytes. Increases nphils, decreases lymphocytes, monocytes, eosinophils, and basobhils.
End result is a decrease in cytokine release, including decreases in IL-2 and TNF-a
decreases size of lymph nodes and spleen
Given in higher doses, using a “pulse” regimen
Cyclosporine
Class: Antirejection antibiotics
MOA: Bind to cyclophilin and inhibit calcineurin. Calcineurin is necessary for the activation of NFAT (T-cell specific transcription factor involved in synthesis of interleukins) which decreases the release of IL-2 –> decrease T cell proliferation.
Tacrolimus
Class: Antirejection antibiotics
MOA: Bind to FK-binding protein and inhibit calcineurin. Calcineurin is necessary for the activation of NFAT (T-cell specific transcription factor involved in synthesis of interleukins) which decreases the release of IL-2 –> decrease T cell proliferation.
Everolimus
MOA: MTOR inhibitor which is an intracellular signaling molecule that increases cell division, bioenergetics, and facilitates angiogenesis.
Synergy with drugs that damage DNA.
PK: oral, metabolized by CYP3A4
Substrate for P glycoprotein.
Side effects: hypersensitivity, increased risk of lymphomas and infection, angioedema, kidney arterial and venous thrombosis.
Temsirolimus
MOA: MTOR inhibitor which is an intracellular signaling molecule that increases cell division, bioenergetics, and facilitates angiogenesis.
Synergy with drugs that damage DNA.
PK: oral, metabolized by CYP3A4
Substrate for P glycoprotein.
Rituximab
MOA: MAB vs. CD20.
Use: B cell non hodgkin’s lymphoma
Resistance: Changes in target protein
PK: IV administration; long half lives (detectable 3-6 months after completion of treatment)
Toxicity: infusion reactions (77% for rituximab), other hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis, HAMA, infections (especially reactivation of TB)
Cardiac arrythmias, and tumor lysis syndrome
Ibritumomab
MOA: MAB vs. CD20.
Use: B cell non hodgkin’s lymphoma
Resistance: Changes in target protein
PK: IV administration; long half lives (detectable 3-6 months after completion of treatment)
Toxicity: infusion reactions (77% for rituximab), other hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis, HAMA, infections (especially reactivation of TB)
Cardiac arrythmias, and tumor lysis syndrome (likely birth defects)
Tositumomab
MOA: MAB vs. CD20.
Use: B cell non hodgkin’s lymphoma
Resistance: Changes in target protein
PK: IV administration; long half lives (detectable 3-6 months after completion of treatment)
Toxicity: infusion reactions (77% for rituximab), other hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis, HAMA, infections (especially reactivation of TB)
Cardiac arrythmias, and tumor lysis syndrome (likely birth defects)
Alemtuzumab
MOA: MAB vs. CD52.
Use: B cell chronic lymphocytic leukemia.
Resistance: Changes in target protein
PK: IV administration; long half lives (detectable 3-6 months after completion of treatment)
Toxicity: infusion reactions (77% for rituximab), other hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis, HAMA, infections (especially reactivation of TB)
Cardiac arrythmias, and tumor lysis syndrome, cough, tightness in chest
Denileukin Diftitux
Fustion protein that has diptheria toxin coupled to IL-2–> diptheria toxin catalyzes the ADP-ribosylation of elongation factor-2 –> inhibits protein translation by inactivating EF2.
Goal is to kill cells expressing IL-2 receptors (activated T cells, B lymphocytes, and mphages)
Use: T cell lymphoma
Resistance: Changes in target protein
PK: IV administration; long half lives (detectable 3-6 months after completion of treatment)
Toxicity: infusion reactions (77% for rituximab), other hypersensitivity reactions: fever, muscle aches, headaches, rashes, anaphylaxis, HAMA, infections (especially reactivation of TB)
Interleukin 2
MOA: induces and expands a T-cell response to tumor cells.
Used along or w/ adoptive cellular therapy (LAK or CIK)
Short half life (13 min.) –> either continuously infused or given as multiple intermittent daily doses.
Side effects: cytokine storm = inflammation, vascular leak; fever/chills, diarrhea, weight gain, or hand-foot syndrome
serious toxicities: thrombocytopenia, shock, respiratory distress, coma, and fatal hypotension.
IFN-a
3 MOA’s- 1.) Decrease the production of fibroblast growth factor (FGF). FGF is angiogenic.
- ) Inhibition of cell division of both normal and tumor cells
- ) increases class I MHC expression on tumor cells –> increased activity of cytotoxic T lymphocytes
Side effects: flu-like symptoms, hypotension, myelosuppression, depression
TNF-a
MOA: Similar to IL-1. Cause fibroblast proliferation, chemokine induction (IL-6, IL-8), T and B cell activation. Causes a decrease in rate of proliferation of tumor cells while sparing normal cells.
PK: Intra-arterial administration due to extremely short half-life and toxicity
Toxicity: Malaise and flu-like sx (severe and dose limiting), can cause hemorrhagic necrosis.