31 & 32 - Common Cancer Drugs Flashcards
alkylating agents - general what are they
strong electrophiles that form pos charged intermediates w/ target molecules and cause DNA damage
alkylating agents - mechanism
inhibit DNA synth / cell division by covalent attachment at 2 points
crosslinks DNA > cytotoxicity
example class and drug of alkylating agents
nitrogen mustards > cyclophosphamide
cyclophosphamide - category
alkylating agent > nitrogen mustard
cyclophosphamide uses
lymphoma regimens, breast cancer, ovarian cancer, some kinds of lung cancer
cyclophosphamide - AEs
myelosuppression (dose limiting)
alopecia, immunosuppression, cystitis
anitmetabolites - what are they
structurally related to natural compounds, compete for normal metabolites
folate antagonist mechanism
block biosynth of fully reduced tetrahydrofolic acid
example of folate antagonist
methotrexate
methotrexate mech
competitively inhibits folic acid binding to dihydrofolate reductase > death due to thymidylate and purine blockage; s-phase specific agent
uses of methotrexate
curative regimen for ALL, trophoblastic choriocarcinoma, Burkitt’s
methotrexate AEs
myelosuppression - dose limiting
renal insufficiency - c/i in pts w/ renal impairment
rescue drug for myelosuppression due to methotrexate
leucovorin
purine analogue mechanism
prevent biosynth of purine precursors
get incorporated into RNA/DNA > fraudulent nucleic acids made
require activation - “lethal synthesis”
ex of purine analogue
thioguanine (a thiolated purine analogue)
use of thioguanine
AML, ALL, CML
AEs of thioguanine
myelosuppression
ex of pyrimidine analogue
5-fluorouracil (halogenated pyrimidine)
uses of 5FU
CA of breast, stomach, COLON, rectum, pancreas, liver, ovary
short story: lots of solid tumors
major AE of 5FU
myelosuppression
hydroxyurea - mech
inhibits ribonucleoside diphosphate reductase
hydroxyurea - use
myeloprolif syndromes
CML
AEs of hydroxyurea
myelosuppression
anticancer abx - general mechanism
inhibit nucleic acid synth by blocking DNA replication or transcription either by direct binding to nucleic acid or polymerizing enzyme
ex of anthracycline (anticancer abx)
doxorubicin
doxorubicin mech
intercalating agent - insert btwn DNA base pairs, S-phase specific
use of doxorubicin
CA of breast, ovary, endometrium, bladder, thyroid, lung
bottom line: solid tumors
AEs of doxorubicin
cardiotoxicity (unique)
myelosuppressive (major)
bleomycin mech
strand scission - cut phosphate backbone
use of bleomycin
potentially curative in combo for testicular CA;
Hodgkin’s and non-Hodgkin’s lymphoma
AEs of bleomycin
lung tox (fibrosis) skin toxic
mech of platinum coordination complexes
electrophile that forms strong coordination complexes w/ DNA (guanine)
use of cisplatin
curative for testicular cancer
AEs of cisplatin
renal tox
2 subcategories of plant derived cancer drugs
vinca alkaloids
taxanes
vincristine mech
binds to tubulin and blocks polymerization > M phase specific agent
use of vincristine
curative for ALL, hodgkins and NHL
AEs of vincristine
neuro toxicity (dose limiting)
ex of taxane
paclitaxel
mech of paclitaxel
binds to beta tubulin and antagonizes MT diasassembly
use of paclitaxel
cisplatin refractory metatstatic ovarian and breast CA
AEs of paclitaxel
myelosuppressive, myalgias, stocking/glove sensory neuropathy
topotecan mech and class
camptothecin analog
binds to topoisomerase I, ssDNA breaks
use of topotecan
ovarian and small cell lung CA
AEs of topotecan
neutropenia
etoposide mech
complex w/ topoisomerase II, dsDNA breaks
use of etoposide
testicular cancer
AEs of etoposide
causes leukemia w/ chromosomal translocation
uses of prednisone for cancer
used to induce remission in ALL
used to treat both Hodgkin and NHL
destroys lymphocytes
what did estrogens used to be used for in cancer?
prostate cancer
tamoxifen
estrogen agonist (SERM) - binds but not transcriptionally active first line therapy for ER+ breast cancer
use of GnRH agonists and antagonists
prostate cancer - leuprolide is equivalent to orchiectomy in terms of response
examples of GnRH agonists
leuprolide
histerelin
nafarelin
goserelin
examples of GnRH antagonists
abarelix *(no testosterone flare)
triptorelin
aromatase inhibitors mech
stop extra-adrenal synth of estrogen in other tissues
ex of aromatase inhib
anastrozole
use of anastrozole
adv ER and PR pos breast cancers
aminoglutethimide
first aromatase inhib, largely replaced by newer ones that dont block hydrocortisone synth
exemestane
irreversible inhib of aromatase
imatinib (Gleevic)
tyrosine kinase inhib targeted to PDGF-R
good for inhibiting Philadelphia chromosome product in CML and c-kit (in GI stromal tumors)
lots of side effects - basically platelet like bleeding, fever/flu sx
bevacizumab (avastin)
ab against VEGF that inhibits angiogenesis
used in colorectal cancer, non-small cell lung cancer, some breast cancers
bortezomib
reversible inhibitor of proteasome (stop breakdown of cell cycle regulators)
used in multiple myeloma and relapsed mantle cell lymphoma
