Chemo Drugs - Cell cycle specific

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  1. Fluoropyrimidines
    • S phase Folate antagonists
    • Capecitabine/5-FU
    • •Diarrhea, nausea, vomiting, and stomatitis
    • •Myocardial infarction, angina, dysrhythmias, cardiac arrest, cardiac failure and ECG changes
    • Capecitabine
    • •Myelosuppression: Lymphopenia in 94% of patients
    • •Hand-foot syndrome (45%): pain, redness, scaling or shedding of the skin of the palms and soles.
    • •Fatigue, anorexia, paraesthsia, & headache
    • 5-FU
    • •Myelosuppression: nadir 7-14 days, recovery usually rapid
    • •Skin: Alopecia, maculopapular rash of extremities
    • •CNS: somnolence and cerebellar ataxia occurs with about 1% incidence.
    • •Ocular: conjunctivitis, lacrimation, blepharitis, and photophobia.
    • Cytarabine
    • Side effects:
    • •Conjuctivitis/corneal toxicity: Prevent with steroid eye drops
    • •High dose: cerebellar toxicity--ataxia
  2. Hydroxyurea
    • •Mechanism of Action:
    • –S phase dependent
    • –Enzyme that inhibits ribonucleotide reductase which is necessary for DNA synthesis
    • •Clinical Use: leukemia, myelodysplasia
    • •Side effects
    • –Myelosuppression
    • –Skin: rash, hyperpigmentation, pruritus
    • –Radiation recall
  3. Vinca Plant Alkaloids
    • M Phase inhibitor
    • •Plant-based chemicals block cell division by inhibiting microtubule assembly (spindle fibers, made of microtubules, help separate the chromatids during cell division)
    • •Examples: Vincristine, Vinorelbine, Vinblastine
    • •Side effects: neuropathy, vesicant
  4. Taxanes
    • M Phase Inhibitor
    • •Plant- based compounds
    • •Increase stability of microtubules: prevents the separation of chromatids during mitotic anaphase
    • •Examples: paclitaxel, docetaxel
    • •Side effects: myelosuppression, neuropathy, fluid retention
  5. Nab Paclitaxel
    • •FDA approved in January 2005
    • •Albumin facilitates the administration of water-insoluble compounds
    • •Allows delivery of a 49% higher dose of paclitaxel
    • •Side effects: neuropathy
  6. Ixabepilone
    • •Semisynthetic analogue of epothilone B
    • •Mechanism
    • –Binds to beta-tubulin
    • –Arrests tumor cells in the G2-M phase of the cell cycle triggering tumor cell apoptosis
    • •Low susceptibility to tumor resistance mechanisms (ie efflux pumps)
    • •Toxicity: neurologic
  7. Aspariginase
    • G1 Phase inhibitor
    • •Mechanism: hydrolyzes circulating L-asparagine to aspartic acid and ammonia resulting in inhibition of protein synthesis
    • •Clinical use: ALL
    • •Resistence: MDR
    • •Side effect:
    • –Hypersensitivity reaction
    • –Decreases clotting factors (IX, Xi, protein C and S, antithrombin III, and fibrinogen)
    • –Pancreatitis
    • –Neurologic toxicity
    • –Fever, chills, nausea, vomiting
  8. Topoisomerase inhibitors
    • G2 Phase Inhibitors
    • Topoisomerase: enzyme essential to maintain the topology of the DNA.
    • •Resistance: altered target enzyme
    • •Inhibition prevents the normal function of DNA: transcription, replication and repair.
    • •Type I: camptothecins—irinotecan (GI) and topotecan (ovarian)
    • •Type II: anthracyclines (breast, leukemia) and epipodophylotoxins (naturally appearing) etoposide (testicular).
    • •Side effects: primarily GI--diarrhea
  9. Anthracyclines
    • G2 Phase inhibitor
    • •Mechanism – Topoisomerase II inhibitor
    • •Examples: Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone
    • •Side effects
    • –N/V
    • –Cardiotoxicity:
    • •Acute: arrhythmias, pericarditis, myocarditis
    • •Chronic: CHF, dilated cardiomyopathy
    • –Red-orange urine discoloration
    • –Radiation recall skin reaction
    • –Mitoxantrone: bluish discoloration of sclera, urine, and finger nails; Less cardiotoxicity and N/V than doxorubicin
  10. Liposomal Doxorubicin
    • •Liposomal formulation evades detection and destruction by the immune system
    • –increases the time the drug is in the body
    • – majority of the drug stays inside the liposome while in the blood (at least 90%).
    • •Side effects
    • –Hand-Foot Syndome (HFS)
    • – Mouth sores
  11. Podophyllotoxin
    • •Plant-derived compounds are primarily extracted from Podophyllum peltatum (American mayapple).
    • •Prevent cancer cells from entering the G1 phase and affect DNA synthesis.
    • •Examples: etoposide and teniposide
    • •Side effects: secondary acute myelogenous leukemia (< 5 years)
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Chemo Drugs - Cell cycle specific
Chemo Drugs
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