Lung Cancer Pharm Flashcards
EGFR mutations are evident in a significant number of what types of cancer?
Adenocarcinoma
High risk of bleeding in squamous cell lung cancer associtated with what drug?
Bevacizumab
What is the significance of activating a tyrosine kinase receptor in a cancer cell
If the ligand is bound by the receptor, transphosphorylation of two tyrosine residues occurs and this signal can be transduced to the nucleus where it effects transcription that can cause uncontrollable growth/avoidance of apoptosis.
TKIs try to prevent this
Resistance to Tyrosine Kinase Inhibitors can occur how
Via EGFR mutation which leads to
- Change in binding site receptor
- compensatory phosphorylation of the Tyr Kinase binding site via MET, HGFR
- or HGF taking assuming an independent role in signaling
What are some other ways that cells can be insensitive to TKI
Via proliferative signals arising from downstream events via KRAS or BRAF mutations
EML4-ALK Translocation
Fuses the EML4 and ALK genes leads to activation of the Mek/Erk pathway and cell proliferation
Why is VEGF a good drug target?
Prevents good vasculature from reaching the tumor site
Genetic testing for KRAS, EGFR, and ALK rearrangement have become necessary for adherence to treatment guidelines
truth
EGFR and ALK testing only recommended for ppl with what type of tumors
Adenocarcinoma
The US preventative service task force recently suggested what
smokers age 55-80 with over 30 pack year history of smoking should receive low dose CT scans to look for possible tumors
What process is sued to test for EGFR mutations
DNA sequencing
What process is used to test for ALK gene rearrnagement
FISH
ALK rearrangements are more common in smokers or non-smokers
non-smokers
Treatment plan for SCLC
Metastasis ocurs early in small cell lung cancer to chemotherapy is the only option
NSCLC treatment
surgical resection if there has been no metastasis. Use chemo in adjuvant role when you need to reduce the bulk of the tumor prior to surgery and eradiate micrometastasis
Prevent growth and metastasis
Standard chemo for SCLC
Etoposide + Cisplatin or Carboplatin
NSCLC treatment
Cisplatin and Paclitaxel
AND EGFR TKI’s for pts with +EGFR genetic test
Maintenance therapy for NSCLC pts who have responsive tumors
Pemetrexed
What are the two nitrogen mustards?
Cyclophosphamide and Ifosfamide
Mechanism of action for cyclophosphamide/Ifosfamide
Bind to the N7 of Guanine and Alkylate DNA producing inter/intra strand crosslinks that prevent DNA replication
Ifosfamide differs from cyclophosphamide in regards to adverse effects how?
No risk of pulmonary fibrosis and less renal toxicity
WHAT MUST BE GIVEN WITH Cyclophosphamide
Mesna…protects against acrolein product and prevents bladder tumors and urotoxicity
Platinum drugs are
Cisplatin and Carboplatin
Platinum drugs MOA
Same as Nitrogen Mustards (cyclophosphamide and Ifosfamide)
Cisplatin Toxicity
Renal, ototoxic, peripheral neuropathy
Carboplatin toxicity
myelosuppresive, ANEMIA, INFECTION
Folic Acid Analogs
Methotrexate, Pemetrexed
How do methotrexate and pemetrexed work?
Dihydrofolate reductase inhibition, inhibits DNA synthesis
Give what with methotrexate and pemetrexed?
Leucovorin- causes metabolic rescue
What kind of drug is Gemcitabine and how does it work>
Pyrimidine analog, DNA polymerase inhibitor causing inhibition of chain elongation
Toxicity associated with Gemcitabine?
“Hand-Foot” syndrome
The two vinca alkyloids are
Vincristine and Vinorelbine
Vinca alkyloids MOA
bind to beta tubulin to cause metaphase arrest and apoptosis. Prevent microtubule assembly.
Vincristine adverse effects
GI stasis, impaction
Intrathecal admin can be fatal, neurotoxicity
Camptothecin analogs
irinotecan and topoteca
How do irinotecan and topotecan work?
They stabilize DNA topoisomerase I cleavable complex causing single and double strand DNA breaks
Toxicity of Camptothecin analogs
extrvasational toxicity (fluid leaking), GI toxicity,
Etoposide mechanism
form complex with topoisomerase II and DNA
BBW for Etoposide
myelosuppression, bleeding, opportunistic infection
Paclitaxel
Bind to beta tubulin to prevent microtubule disassembly.
Bevacizumab
anti-VEGF, binds to VEGF, prevents receptor activation, anti angiogenesis/neovascularization
Big side effect for Bevacizumab
hemorrhage (can be life threatening esp with squamous cell
Erlotinib
Reversible inhibitor for EGFR
WHat do you always give with Doxorubicin to relieve cardiotoxicity
Dexroxazone…iron chelator
What do you give with Cisplatin and carboplatin q
Amifostine
