PHARM LUNG CANCER Flashcards
MOA carboplatin
platinum drugs that form DNA intra-strand cross links
MOA cisplatin
platinum drug that forms DNA intra-strand crosslinks
MOA of ifosfamide
forms intra and interstrand cross links
MOA of cyclophosphamide
pro drug alkylating agent that forms DNA cross-links, resulting in inhibition of DNA synthesis and function
MOA of doxorubicin
intercalator, free radicals bind to DNA causing strand breakage; inhibits topoisomerase II
Etoposide MOA
inhibits topoisomerase II, resulting in DNA damage
irinotecan/topotecan MOA
inhibits topoisomerase I, resulting in DNA damage
Gemcitabine MOA
DNA polymerase inhibitor
MOA of pemetrexed
Dihydrofolate reductase inhibitor
Paclitaxel MOA
prevent microtubule disassembly into tubulin monomers
Vincristine/Vinorelbine MOA
prevent assembly of tublin dimers into microtubules
Erlotinib MOA
EGFR TK reversible inhibitor
Crizotinib MOA
reversible multiple TK inhibitor
Bevacizumab MOA
antibody to VEGF resulting in inhibition of tumor vascularization
who gets screened w/ CT for lung cancer?
pts 55-80 w/ 30 pack-yr hx of smoking who quit 15 yrs prior
radiation exposure risk is greater than benefit of finding tumors early
which mutations in lung cancers do you want to test for?
look for EGFR and EML4-ALK mutations in adenocarcinomas
what is the indication for erlotinib?
only used in adenocarcinomas w/ EGFR overexpression
what is the indication for crizotinib?
used in adenocarcinomas with EML4-ALK mutations
what is the indication for bevacizumab?
used in adenocarcinomas
what is a very common adverse effect of erlotinib?
Rash
How would you treat a severe rash caused by TKIs?
reduce dose of chemo agent
- protective sun lotion
- steroid creams
- consider tetra cycline as pre-emptive therapy
what are 5 general ways that explain the resistance to conventional chemotherapy agents
- mutations in target
- decreased metabolic activation
- decreased metabolic degradation
- increased repair
- MDR efflux pump
Name some drugs that have the MDR efflux pump
doxorubicin
vinca alkaloids
taxanes
etoposide
which tumor genotype are you looking for in adenocarcinoma which may increase sensitivity to the drug?
exon 19 or L858R in ATP binding site of EGFR
which tumor genotype are you looking for in an adenocarcinoma which may decrease sensitivity to erlotinib?
T790M in ATP binding site of EGFR
what are some strategies that will mitigate overdiagnosis?
- screen only pts w/ appropriate risk
- change threshold for positive test
- change terminology (use of the word cancer)
- reduce freq. of screening
- reduce low-yield diagnostics
- improve safety and efficacy of screening tools
which 3 cancer chemotherapy drugs have a dose limiting toxicity other than myelosuppression?
Cisplatin–>renal tubular damage, failure, MLS
Vincristine–>neurotoxicity, ANS dysfunction, GI status (impaction)
etoposide–>myelosuppression, hematologic toxicity
which mutations are more common in smokers?
KRAS mutations
which mutations are more common in never smokers?
EGFR mutations
what are the potential downsides to blocking formation of new blood vessels in tumors?
- prevent chemodrugs from getting to their target
2. induce more aggressive cells that have increased capacity to spread
how do we test for EGFR mutations?
DNA sequencing
how do we test for ALK gene rearrangement testing?
FISH
what is the standard treatment for SCLC?
Etoposide + Cisplatin or Carboplatin
what is the standard treatment for NSCLC?
Cisplatin AND one of the following: paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan or pemetrexed
intrathecal administration of what class of drugs is fatal?
vinca alkaloids
which chemo agent has this side-effect profile: interstitial lung disease, stomach or intestinal perforation, corneal perforation/ulceration and rash?
erlotinib
how do you want to take erlotinib?
on an empty stomach because it has variable bioavailability with food
which chemo drug has this side-effect profile?
- Visual disorders
- Edema
- GI toxicity (N/V/D/C)
crizotinib
which chemo drug has this side-effect profile?
LIFE-THREATENING BLEEDING (post-surgical)
Hemorrhage (gastric perforation)
HTN (arterial thromboembolism)
Alopecia
Asthenia, Dizziness, Headache
fistulas
Bevacizumab
which chemo drug do you absolutely avoid using on squamous cell carcinoma of the lung?
Bevacizumab