Term
| two broad categories of cancer chemotherapy |
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Definition
| cytotoxic agents - nonspecifically inhibit replication; targeted anticancer drugs - inhibit certain proteins |
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Term
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Definition
| produce rapid reduction in tumor cell burden and thereby produce a symptomatic response; ie - acute lymphocytic leukemia |
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Term
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Definition
| complete or extend initial remission (different drugs than induction) |
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Term
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Definition
| sustain remission as long as possible; less-frequent/different drugs |
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Term
| cytotoxic antineoplastic drugs |
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Definition
cell cycle-specific and cell cycle-non specific
non - all DNA alkylating and most DNA intercalating drugs
Specific - Temsirolimus, DNA synthesis inhibitors; Bleomycin, etopside and teniposide; mitotic inhibitors |
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Term
| cyclin processing (order of 4 major cyclins) |
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Definition
cyclins prevent progression to the next step of the mitotic pathway
A - end of S to end of G2
B - beginning of G2 to Beginning of M
D - G1
E - S to G2 |
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Term
| Limitations of cancer chemotherapy |
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Definition
| drug resistance, drug toxicity, inability to surpress metastasis |
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Term
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Definition
p-glycoprotein pump and multidrug-resistance proten - both act to remove drugs from cells preventing their efficacy
MRP - conjugates with glutathione before excretion
topoisomerase mutations; dihydrofolate reductase mutation; antiapoptotic protein expression modulation
increased tumor cell repair
overexpression of target enzymes |
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Term
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Definition
non-specific replication inhibitors; nausea and vomiting from medulla; bone marrow suppression
alopecia - hair loss
organ toxicity may occur as well
neuro and pulmonary toxicity have not preventative treatment
renal toxicity can be prevented with mannitol and sodium thiosulfate
minimize with BM transplant and hG-CSF |
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Term
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Definition
| bone marrow suppresion - results in leukopenia/thrombocytopenia and anemia |
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Term
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Definition
cure - 10 years disease free survival
control - prevent progression
palliation - improve symptoms |
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Term
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Definition
| to supplement other treatments (surgery) |
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Term
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Definition
| given prior to surgery to reduce tumor |
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Term
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Definition
| lower doses - to control the growth and prolong remission |
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Term
| what allows a cell to survive chemo? |
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Definition
| if it is slowly dividing then it is more likely to survive - Tumor growth fraction can determine this |
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Term
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Definition
| cells die according to a proportion of the total that are present; follows first-order kinetics |
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Term
| cancer treatment scheduling |
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Definition
| 21 days apart to allow regrowth of normal tissues |
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Term
| problem with alkylating agents |
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Definition
| are mutagenic and can cause further neoplasms |
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Term
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Definition
| teratogenesis (1st trimester) |
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Term
| antimetabolites (DNA Synth Inhibitors) |
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Definition
Two types of these cell-cyle specific Drugs:
1. analogues that terminate DNA elongation
2. Attack enzymes that prevent substrate creation for DNA synthesis
folate antagonists;
purine antagonists
pyrimidine antagonists
ribonucleotide reductase inhibitor |
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Term
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Definition
| methotrexate and pemetrexed (acts on several tetrahydrofolate dependent enzymes) |
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Term
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Definition
inh dihydrofolate reductase and therefore decreases tetrahydrofolate and purine/thymidine synthesis
adverse effects - add leucovorin (fully activated folic acid) |
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Term
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Definition
purine base analogues:
6-mercaptopurine
6-thioguanine
Purine Nucleoside/tide analogues
Cladribine
fludarabine
clofarabine
nelarabine |
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Term
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Definition
mercaptopurine/thioguanine -
converted to nucleotide form
inhibit IMP converstion to AMP/GMP (enzyme is inosine monophosphate dehydrogenase)
Mercaptopurine - inhibits de novo purine synthesis (glutamine phosphoribosyl pyrophosphate amidotransferase)
allopurinol is frequently administered to cancer patients due to large build up of uric acid metabolites - mercaptopurine is degraded by xanthine oxidase and therefore must be reduced in dosage if allopurinol is administered |
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Term
| purine nucleoside analogues |
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Definition
Cladribine (Leustatin)
Fludarabine (Fludara)
Clofarabine (Clolar)
Nelarabine (Arranon)
all are halogenated purine nucleoside analogues which are incorporated into nascent DNA causing termination of replication |
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Term
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Definition
cytarabine and fluoracil
others - floxuridine, capecitabine, gemcitabine |
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Term
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Definition
| purine/pyrimidine analogues |
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Term
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Definition
| uracil analobue that is converted to FdUMP which inhibits thymidylate synthase preventing dTMP formation |
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Term
| ribonucleotide reductase inhibitor |
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Definition
hydroxyurea - prevents conversion from ribonucleotides to deoxyribonucleotides
uses - chronic myelogenous leukemia, ovarian cancer, melanoma |
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Term
| agents that modify DNA structures |
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Definition
cross-link DNA
-alkylating agents
-platinum compoounds
Intercalate DNA
-antracycline drugs
others |
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Term
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Definition
must be activated; electrophiles that attack DNA nucleophilic sites and leave alkyl groups (guanine susceptible)
usually bis-alkylate potential = DNA cross-lining == DNA BREAKAGE = DNA cell death
NOTE: all are mutagenic and carcinogenic
cell cycle non-specific
nitrogen mustards
-cyclophosphamide
nitrosourea drugs
others
1) Nitrogen mustards
Mechlorethamine (Mustargen)
Cyclophosphamide and ifosfamide
(Cytoxan and Ifex)
Chlorambucil (Leukeran)
Melphalan (Alkeran)
2) Nitrosourea drugs
Carmustine (BCNU, Carmubris)
Lomustine (CCNU, Belustine)
Streptozocin (Zanosar)
3) Other alkylating drugs
Busulfan (Myleran)
Dacarbazine (DIC, DTIC-Dome)
Temozolomide (Temodal)
Mitomycin (Mutamycin) |
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Term
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Definition
| alkylating agent: treat with MESNA if this causes Cystitis (bladder inflammation) |
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Term
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Definition
(-platin) cross-link DNA; nephrotoxicity is major toxicity; no alkyl group
Cisplatin (Platinol)
Carboplatin (Paraplatin)
Oxaliplatin (Eloxatin)
note: amifostine co-administration limits nephrotoxicity |
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Term
| drugs that intercalate DNA |
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Definition
1. insert between paired bases causes unwinding
2. inhibits topoisomerase II
3. formation of free radicals
tox
CHF (free radicals cause from doxyrubicin) - reduce with dexrazoxane
Bleomycin = pulmonary fibrosis
1. Anthracycline drugs
Doxorubicin (Adriamycin)
Daunorubicin (Cerubidine)
Idarubicin (Idamycin)
Mitoxantrone (Novantrone)
2. Other DNA intercalating drugs
Bleomycin (Blenoxane)
Dactinomycin (Cosmegen) |
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Term
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Definition
interfere with enzyme function blocking ligation of nicked strands = permenant strands (S phase specific)
1. Camptothecin analogues
(Topoisomerase I inhibitors)
1) Irinotecan (Camptosar)
2) Topotecan (Hycamtin)
2. Epipodophyllotoxins
(Topoisomerase II inhibitors)
1) Etoposide (VePesid)
2) Teniposide (Vumon)
3. Amsacrine
(Topoisomerase II inhibitor)
note: topoisomeras I fixes single stranded and II fixes double stranded DNA |
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Term
| mitotic inhibitors (microtubule) |
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Definition
Mitosis specific
vinca alkaloids - prevent tubulin polymerization (metaphase)
vincadictive people make society stagnant
taxanes - inhibit depolymerization (anaphase)
Taxes prevent society from falling apart
can cause neurotoxicity (due to microtubule function in neurons)
1. Vinca Alkaloids
1) Vincristine (Oncovin)
2) Vinblastine (Velban)
3) Vinorelbine (Navelbine)
2. Taxanes
1) Paclitaxel (Taxol)
2) Docetaxel (Taxotere)
3) Abraxane |
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Term
| hormones and their antagonists |
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Definition
breast cancer
estrogen antagonists
aromatase inhibitors
prostate cancer
androgen antagonists
GnRH receptor modulators
Corticosteroids |
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Term
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Definition
hormonal therapy - growth of breast is stimulated by estrogen (affecting cell growth and proliferation)
inhibit estrogen production (aromatase inhibitors)
blockade of receptors (anti-estrogen drugs) |
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Term
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Definition
tamoxifen; toremifene;
leaves produce transcriptionally inactive
Indications: Estrogen receptor-positve BC
may cause endometrial cancer (only 5 years of use), associated with hot flashes and vaginal bleeding |
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Term
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Definition
decreases circulating estrogen
indications: advanced and metastatic breast cancer in postmenopausal women
well tolerated (hot flashes/vaginal bleeding)
1) Aminoglutethimide (Cytadren)
2) Anastrozole (Arimidex)
3) Letrozole (Femara)
4) Exemestane (Aromasin) |
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Term
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Definition
prostate cancer stimulated by androgens which are produced under stim from leuteinizing hormone
GnRH inhibitor - inhibits LH release
Androgen angatonist - compete with receptor
adverse effects - impotence, hot flashes |
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Term
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Definition
corticosteriods
prednisone
dexamethasone
inhibit proliferation and cause atrophy of lymphoid tissue
lymphocytic leukemiase
lymphomas
multiple myeloma |
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Term
| tyrosine kinase inhibitors |
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Definition
block tyrosine kinase enzymatic activity to prevent downstream activation of cell proliferation pathways
Imatinib (Gleevec)
Dasatinib (Sprycel)
Nilotinib (Tasigna)
Sunitinib (Sutent)
Sorafenib (Nexavar)
Gefitinib (Iressa)
Erlotinib (Tarceva)
Lapatinib (Tykerb) |
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Term
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Definition
| tyrosine kinase inhibitors; chronic myelogenous leukemia is targed with this drug |
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Term
| targeted anticancer drugs |
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Definition
Monoclonal antibodies
hematologic malignancies overproduce cell-surface markers
solid tumors over produce growth factor receptors
antibodies against both
less toxic
Rituximab (Rituxan)
Alemtuzumab (Campath)
Gemtuzumab -ozogamicin (Mylotarg)
Trastuzumab (Herceptin)
Cetuximab (Erbitux)
Panitumumab (Vectibix)
Bevacizumab (Avastin) |
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Term
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Definition
Antimetabolites:
Methotrexate
6-Mercaptopurine
6-Thioguanine
5-Fluorouracil
Hydroxyurea
Agents that modify DNA structures:
Cyclophosphamide
Cisplatin
Carboplatin
Doxorubicin
Daunorubicin
Bleomycin
Topoisomerase inhibitors:
Irinotecan
Topotecan
Etoposide
Microtubule inhibitors:
Vincristine
Vinblastine
Paclitaxel
Docetaxel
Hormonal agents:
Tamoxifen
Anastrozole
Letrozole
Leuprolide
Goserelin
Prednisone
Targeted anticancer drugs:
Imatinib |
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