17. Anti-Cancer Agents Flashcards
Cyclophosphamide
alkylating agent. causes DNA damage in various ways (can cross link DNA strands, bind groups…)
Odansetron
Serotonin receptor blocker, anti-emetic that makes use of alkylating agents much more bearable.
methotrexate
antimetabolite, inhibits DHFR, blocks DNA synthesis, only works in S phase
general, side effects?
nausea, vomiting, alopecia
Leucovorin: with methotrexate?
rescue body cells, still kill cancer cells
5-fluorouracil (5-FU)
binds thymidylate synthase, prevents purine synthesis
Leucovorin with 5-FU?
stabilizes binding to thymidylate synthase, enhances effect
vincristine
binds to protein tubulin, prevents mT assembly, M phase specific. NOT toxic to BM, can be combined with drugs that are
vinblastine
binds to protein tubulin, prevents mT assembly, M phase specific. toxic to bone marrow.
toxicity: vincristine v vinblastine?
vinc: NOT toxic to BM,
vinb: TOXIC to BM
taxol
binds to mTs, prevents normal mitosis
Velcade
proteasome blockade! binds proteosome, abnl proteins build up, apoptosis
Lenolidimide
immunomodulatory in a way we don’t understand. SE = neuropathy
very effective in multiple myeloma
G-CSF, GM-CSF, EPO
hematopoietic growth factors. prevent blood counts from dropping w chemo
IL2
biologic response modifier. give to pts to incr immune response to cancer
rituximab
monoclonal antibody, targets CD20, B cell NHL. then macrophage destroys cell.
5-Azacytidine
DNA methylation can –> cancer. this prevents methylation. tumor suppressor genes that may have been silenced will be turned back on.
biggest class of chemo drugs?
DNA damaging agents
in general, how do these drugs all work?
by inducing apoptosis in various ways
alkylating agents: phase? response curve?
phase non-specific. linear dose response.
alkylating agents associated with high incidence of what?
secondary cancers (esp leukemia, lymphoma, MDS)
cyclophosphamide: has to be activated? by what?
yes by the hepatic p450 system
side effect of cyclophosphamide?
hemorrhagic cystitis. caused by acrolein.
how to prevent cyclophosphamide-induced hemorrhagic cystitis?
MESNA, binds acrolein
secondary malignancies are mos common with what drugs, treatments?
alkylating agents, XRT
what is an antiemetic that can be combined with 5-HT inhibitors like odansetron?
aprepitant. blocks Substance P binding
antimetabolite drugs have to act on drugs in what phase?
S phase
what are ways tumor cells can become resistant to methotrexate?
decreased transport, gene amplification, mutation of DHFR
methotrexate is also used for what?
immunosuppression in other diseases like RA, lupus, to prevent GVHD
Cytarbine (ara-C)
nucleoside analog. inhibit DNA polymerase.
Ara-C: phase specific?
S phase specific
Ara-C most commonly used to treat what?
AML
Ara-C: part of what chemo regimen?
given continuously for 7 days as part of the 7+3 regimen, with daunarubicin.
Ara-C: what side effects?
acute cerebellar toxicity.
topo inhibitors: what do they do?
cause single or double strand breaks.
anthracycline antibiotics: what are the classic drugs of this group?
doxorubicin and daunarubicin
anthracyclines: what do they do?
get right into the DNA strand, inhibit repl and mRNA synth. Topo II inhibitor as well.
anthracycline antibiotics: side effects?
damage to the heart, vesicants. problems with IV sites
Etoposide: mechanism
Topo II inhibitor
Camptotheca: mechanism?
Topo I inh
what can happen if we drive EPO too high with exogenous growth factors?
HTN, stroke
ESA stands for what?
erythropoietin stim agent
benefit of G-CSF?
counts will recover earlier, increases the max dose a patient can tolerate
Gemtuzumab: target, disease?
CD33 (immature myeloid), AML
Rituximab: target, disease?
CD20 (B lymphs), lymphoma
tiuxetan: target, disease?
CD20 (B lymphs), NHL
cetuximab: target, disease?
EGFR, colorectal, head, neck
bevacizumab: target, disease?
VEGF, several
