Drugs for Lung Cancer Flashcards
TKI’s
The “nibs”
Blocks the EGFR pathway which, upon binding of a ligand, dimerizes and through series of pathways, is transducer to the nucleus where effects upon nuclear transcription can lead to cell growth and proliferation.
**Often a gain of function mutation in many cancers.
What is downstream from EFGR?
Kras, Braf, Mek, Erk/MAPK
What does fusion of EML4/ERK do?
Produces activation of the MEK/ERK pathway and cell proliferation.
Are mutations only found in patients who have a history of smoking?
NO
What type of cancer is genetic testing important for?
Adenocarcinoma
What mutations are required to be tested for?
KRAS, EFGR, ALK rearrangement.
Other mutations such as BRAF, MET, etc can also be appropriate.
How do you test for EFGR?
DNA sequencing
How do you test for ALK fusion gene?
FISH
Who are ALK mutations more common in?
Non Smokers
Who are EFGR and mutations more common in?
Non Smokers
What does the US Preventive Services Task Force recommend?
Smokers between 55-80 yrs old with >30yr pack history and those who have quit within the past 15yrs should get low dose CTs of their lungs to look for possible tumors.
Treatment of SCLC
Metastasis occurs early so chemotherapy/radiation is the only option.
Treatment of NSCLC
In early stages, surgical resection if there has been no metastasis.
Tx used in adjuvant, neoadjuvant, or maintenance role to reduce the bulk of the tumor prior to resection, to eradicate micro metastases, and to prevent growth and metastasis.
Pre operative chemo may, however, delay potentially curative surgery.
Metastasis of NSCLC
Usually very early and most commonly to the adrenals, liver, brain and bone.
Standard Chemotherapy for SCLC
Etoposide + Cisplatin or Carboplatin
Standard Treatment for NSCLC
Cisplatin AND Paclitaxel, Gemcitabine, Docetaxel, Vinorelbine, Irinotecan, or Pemetrexed
+EFGR TKIs for patients with EFGR positive testing.
+Bevacizumab for patients with non squamous histology, no brain metastasis, no hemptysis.
Pemetrexed
Methotrexate analog (DHFR inhibitor). Maintainance dosing given for patients with stable or responding disease following 4 cycles of nonpemetrexed-platinium combination therapy.
MOA of Carboplatin, Cisplatin
Forms DNA inter strand cross links and adducts
MOA of Cyclophosphamide
Pro-drug of active alkylating moiety
MOA if Docetaxel
Microtubule stabilizer inhibiting depolymerization
MOA of Doxorubicin.
Intercalator, free radical generator, topo II inhibitor
MOA of Etoposide, VP-16
DNA-topo II complex stabilizer
MOA of Gemcitabine
DNA polymerase inhibitorvia incorporation of triphosphate form during DNA synthesis
MOA of Ifosfamide
Intra and Inter strand crosslinker
MOA of Irinotecan
DNA-topo I complex stabilizer
MOA of Paclitaxel
Microtubule stabilizer inhibiting depolymerization
MOA of Pemetrexed
DHFR inhibitor
MOA of Topotecan
DNA topo I complex stabilizer
MOA of Vincristine, Vinorelbine
Microtubule inhibitor; Tubules disintegrate into spiral aggregates/ protofilaments
Cisplatin Toxicities
Nephrotoxicty, Ototoxicity.
Cyclophosphamide Toxicities
Hemorrhagic Cystitis
Docetaxel Toxicities
Sensory Neuropathy
Doxirubicin Toxicities
Cardiotoxicity in cummulative dose exposure.
Etoposide Toxicities
Alopecia
Vinca Alkaloid Toxicity
Neuropathic Toxicities
Erlotinib
Reversible inhibitor of EFGR Oral administration. CYP Substrate. Smoking increases clearance. Interstitial lung type events can occur. Liver, Kidney problems. Stomach or intestinal perforation. Corneal perforation/ulceration. Rash
Afatinib
Covalent inhibitor of EFGR, HER2, HER4.
Oral administration.
Similar problems of bioavailability and rash like Erlotinib but less overall side effects.
**Rare pulmonary toxicity in Asian ethnicity.
What is a common side effect of EGFR/ TKI
Rash is common and is often used as proof for physicians that the drug has reached effective concentration levels.
