08.26 - Pharmacology of Lung Cancer (Sweatman) - Questions Flashcards
Drug used for non-squamous NSCLC only
Bevacizumab
Which subtype harbors EGFR mutation
Adenocarcinoma
Why no Bevacizumab in Squamous Cell
High risk of bleeding
KRAS mutation can render __ drugs ineffective
Anti-EGFR
In what subtype is EML4-ALK more prevalent
2-7% of NSCLC, more in adeno
What type of patients are likely to have EML4-ALK
Nonsmokers, Light Smoking, Adeno
EML4-ALK produces activation of
MEK/ERK Pathway
Inhibitor of EML4-ALK
Crizotinib
Problem in TKI administration
Orally administered - Must be absorbed
Mutations (4) more common in Non-smokers
EGFR, EML4-ALK, HER2, hMSH2
What percent of patients have actionable mutations
60%
Top 3 mutations, in order, in adenocarcinomas
KRAS, EGFR, ALK
Which subtype of tumor should have mutation testing
Adenocarcinoma
Test for EGFR
DNA seq
Test for EML4-ALK
FISH
Treatment rationale for SCLC
Met occurs early so chemo/radiation is only option
Treatment rationale for NSLC
Surgical recision if early stage, Genetic testing if adeno
Standard treatment for SCLC
Etoposide + Cisplatin or Carboplatin
Standard treatment for NSCLC
Cisplatin + Taxel or other; Maintenance w/ Pemetrexed; Targeted; Bevacizumab if non-squamous
General MOA of Pemetrexed
DHFR inhibitor
General MOA of -platins
Form DNA intrastrand crosslinks and adducts
General MOA of Cyclophosphamide
Alkylating
General MOA of - Taxels
Microtubule stabilizer inhibiting de-polymerization
General MOA of Doxorubicin
Intercalator, Free Radicals, Topo 2 inhibition
General MOA of Etoposide
DNA Topo 2 stabilizer
General MOA of Gemcitabine
DNA polymerase inhibitor
General MOA of Isfosfamide
Cross linker
General MOA of -Tecans
DNA Topo 1 stabilizer
General MOA of Vinca Alkyloids
Microtubule inhibitor
Toxicity of Carboplatin
Blood chemistry dyscrasia
Toxicity of Cisplatin
Nephro- and Oto-toxicity
Toxicity of Cyclophosphamide
Hemorrhagic Cystitis (Mesna is protective), Pulmonary Fibrosis
Toxicity of Docataxel
Sensory neuropathy
Toxicity of Doxorubicin
CHF - Cardiotoxicity
Toxicity of Etoposide
Infection, Alopecia
Toxicity of Gemcitabine
Arthralgia
Toxicity of Ifosfamide
Neurotoxicity, Renal failure (<10%)
Toxicity of Irinotecan
Typical
Toxicity of Paclitaxel
Myalgia and Arthralgia
Toxicity of Pemetrexed
Elevated LFTs and Creatinine
Toxicity of Topotecan
Hyperbilirubinemia
Toxicity of Vinblastine
Neuropathic; Never give intrathecal
Toxicity of Vinorelbine
Neutropenia; Never give intrathecal
2 notable toxicities of Erlotinib
Rash; Interstitial lung-disease-type events
General MOA of Afatinib
Covalent inhibitor of EGRF, HER2, and HER4
2 most notable toxicities of Afatinib
Diarrhea, Rash
Covalent inhibitor of EGRF, HER2, and HER4
Afatinib
Advantage of Afatinib
Less toxic than Erlotinib
Mutation that confers resistance of EGFR to TKI’s
T790M
T790M mutation restores
ATP affinity of EGFR to WT levels
2 notable toxicites of Crizotinib
GI, Visual Disorders
General MOA of Crizotinib
Multi-kinase inhibitor, including ALK
Sims and Diffs in toxicities of Erlotinib and Crizotinib
Both liver and eye; erlotinib rash, much less rash in crizotinib
TKI’s that are CYP substrates
Crizotinib, Erlotinib
Mutation that confers resistance to Crizotinib
G2032R ROS1
MOA of Bevacizumab
Receptor of VEGFR fused to Fc fragment of an antibody - Prevents VEGF from binding its endogenous receptor sites
2 notable toxicities of Bevacizumab
HTN/Thromboembolism; Fistula
What subtype has highest adverse effects with Bevacizumab
Squamous - don’t use