Cancer Chemotherapy Drugs Flashcards
Trastuzumab (herceptin)
First antibody against oncogene
Anti-HER2 growth factor, Ag binding region fused to IgG
Used with chemotherapy: doxorubicin and cyclophosphamide
Better with pertuzumab
Lower death rate and slower progression
Cardiac toxicity
General Side effects of chemotherapy
Teratogenic, mutagenic, carcinogenic
Suppression of bone marrow activity
Reactions on skin and GI tract
Liver toxicity: alkylating agents and antimetsbolites
Neurotoxicity: plant alkaloids
Infection-immunosuppressive
Hemorrhage-toxicity to bone marrow decreased platelets
Imantinib (gleevec)
Treats chronic myeloid leukemia
Tyrosine kinase inhibitor
Sustains remissions of CML
Toxicity: nausea, vomiting, diarrhea, edema, muscle cramps, rash, neutropenia, and thrmobocytopenia
Gefitinib (iressa)
Used for non small cell lung cancer
Especially effective against tyrosine kinases associated with epidermal growth factor
Blocks growth signals mediated by tyrosine kinases
Only 10% have rapid response
Bevacizumab (Avastin)
Tyrosine kinase inhibitor
Targets vascular endothelial growth factor
Inhibits angiogenesis
Sunitinib (sutent)
Newer
Tyrosine kinase inhibitor
Targets vascular endothelial growth factor
Inhibits angiogenesis
Sorafenib (nexavar)
Tyrosine kinase inhibitor
Targets vascular endothelial growth factor
Inhibits angiogenesis
Suberoylanilide Hydroxamic Acid (vorinostat)
Treats epigentics
Histone deacetylase inhibitor
Acetylation of his tones maintain chromatin in an open transcriptionally active reading frame
Reactivate down regulate tumor suppressor genes inhibiting cell growth
Azacytidine and Decitabine
Treat epigenetics
Inhibit methylation of DNA down regulating gene expression
Reactivate tumor suppressor genes inhibiting growth of cancer cells
Methylguanine methyl transferase (MGMT) silencing
MGMT Repairs alkylation damage to DNA
Temozolomide is an alkylating agent
Alkylation maintains chromatin in open frame
Methylation decreases gene expression
Patients with methylated MGMT will be responsive to temozolomide treatment
Dolastron (anzemet)
Palonosetron (aloxi)
Serotonin receptor antagonists
Prevention of nausea and vomiting due to chemo -increase compliance
Side effects: headaches, dizziness, diarrhea and constipation
P has a half life of 40 hours
Dexamethasone
Corticosteroid
Serotonin receptor antagonist
Prevention of nausea and vomiting due to chemo-increase compliance
Side effects: headache, dizziness, diarrhea and constipation
Chlorambucil
Non cycle active alkylating agent Covalently modify DNA base Oral absorption Least toxic of alkylating agents Used for chronic leukemias
Cyclophosphamide
Non Cylce active alkylating agent
Covalently modifies DNA base
Requires metabolic liver activation
Liver toxicity and hair loss are side effects
Carmustin (BCNU)
Non active cycle alkylating agent
Covalently modifies DNA bases
Lipid soluble-crosses BBB
CNS tumors
Busulfan
Non cycle active alkylating agent
Covalently modifies DNA bases
Primarily used for myelosuppression
Relatively little GI tract toxicity
Gemcitabine
Non cycle active alkylating agent
Inhibits DNA synthesis and alters DNA template activity
Effective against solid tumors
Methotrexate
Cycle active antimetabolite Folic acid analog Parent compound is active Renal excretion DNA synthesis inhibitor-S phase Decreases THF production Binds to glutamate to become more water soluble and trapped inside cell-more sensitive Do not administer in cases of renal impairment
Folinic acid
Rescue methotrexate induced host toxicity in normal cells
Systemic
Decrease adverse reactions
Mercaptopurine
Thioguanine
Cycle active antimetabolites
Metabolism is required to nucleotide mono phosphate level
Inhibit DNA synthesis-S phase
Inhibit multiple steps in purine synthesis
5-fluorouracil
Cytarabine
Cycle active antimetabolites
Metabolism is required to nucleoside mono phosphate level
Pyramidine analogs, inhibit multiple steps in Pyramidine synthesis
5FU-hair loss
Folinic acid rescue
Paclitaxel (taxol)
Natural product
Cycle active
Blocks mitosis
Vincristine
Cycle active natural product Vinca alkaloid Inhibit mitosis, metaphase arrest Remission acute leukemia Minimal myelosuppression CNS toxicity progressive and cumulative Weakness, tremors, convulsions
Vinblastine
Cycle active natural product Vinca alkaloids Inhibit mitosis, metaphase arrest Used for Solid tumors, Hodgkin's disease and testicular tumors Toxicity: is myelosuppression Less neuro toxicity
Etoposide
cycle active-s phase natural product
From mandrake plant
Inhibits topoisomerase causing DNA strand breaks
Used for Testicular cancer
Topotecan
Cycle active natural product (s phase)
Topoisomerase inhibitor causing DNA strand breaks
Used for ovarian and lung cancer
Actinomycin D
Non cycle active antibiotic
Inhibits RNA polymerase/RNA synthesis
Used for solid tumors
Very toxic especially bone marrow suppression
Bleomycin
Non cycle active antibiotic Mixture of related drugs Reacts with DNA-strand breaks Used for solid tumors, testicular cancer and lymphomas Pulmonary fibrosis occurs In 2-5%
Doxorubicin (adriamycin)
Cycle active antibiotic Inhibits topoisomerase Cardiac toxicity-arrythmias and congestive heart failure Loss of hair Keep blood levels low and monitor
Mitomycin
Non cycle active antibiotic
Alkylating agent
Used for solid tumors
Prednisone
Corticoid
Induction of remission in leukemia
Tamoxifen
Antiestrogen (estrogen drives cancer proliferation)
Metabolized in liver CYP2D6 to endoxifen the active form
Antidepressants (Paxil and Prozac) also metabolized by CYP2D6 causing decreased metabolism of tamoxifen
Exemestane
Anastrozole
Aromatase inhibitors
Inhibit the metabolism of androstenedione to estrone which is then metabolized to estradiol
Decrease estrogen (estrogen drives cancer proliferation)
Treat many breast cancers that are estrogen receptor positive
Flutamide + leuprolide
Antiandrogen
Leuprolide- analog of leurenizing hormone releasing hormone must be used or a bilateral castration-decrease synthesis and release of gonadotropins by pituitary
Blocks uptake of androgens
Used for metastic prostate cancer-May prolong life
Toxicity:gynecomastia, nausea and vomiting
Cisplatin (oxaplatin, carboplatin)
MOA: similar to alkylating agents
Damages DNA
Non cycle active
IV administration
Excreted in urine
Toxicity: renal toxicity minimized by hydration, mannitol diuresis
Used for a variety if solid tumors: head/neck ovarian, bladder and testicular
Hydroxyurea
Cycle active-S phase
Inhibits ribonucleotide reductase which Catalyzes the metabolism of ribonucleotidrs to deoxyribonucleotides
Inhibits DNA synthesis
Mechanisms of cancer resistance
- Inaccessibility of target site
- catabolism of drug
- decreased uptake
- BBB-must be lipid soluble - Lack of metabolic activation by tumor
- Target site becomes non critical
- altered receptor
- alternative metabolic pathway
- precursor concentration overrides
- long g1 less dividing
