Drugs for Lung Cancer

Question 1

TKI’s

Answer 1

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.

Question 2

What is downstream from EFGR?

Answer 2

Kras, Braf, Mek, Erk/MAPK

Question 3

What does fusion of EML4/ERK do?

Answer 3

Produces activation of the MEK/ERK pathway and cell proliferation.

Question 4

Are mutations only found in patients who have a history of smoking?

Answer 4

NO

Question 5

What type of cancer is genetic testing important for?

Answer 5

Adenocarcinoma

Question 6

What mutations are required to be tested for?

Answer 6

KRAS, EFGR, ALK rearrangement.

Other mutations such as BRAF, MET, etc can also be appropriate.

Question 7

How do you test for EFGR?

Answer 7

DNA sequencing

Question 8

How do you test for ALK fusion gene?

Answer 8

FISH

Question 9

Who are ALK mutations more common in?

Answer 9

Non Smokers

Question 10

Who are EFGR and mutations more common in?

Answer 10

Non Smokers

Question 11

What does the US Preventive Services Task Force recommend?

Answer 11

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.

Question 12

Treatment of SCLC

Answer 12

Metastasis occurs early so chemotherapy/radiation is the only option.

Question 13

Treatment of NSCLC

Answer 13

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.

Question 14

Metastasis of NSCLC

Answer 14

Usually very early and most commonly to the adrenals, liver, brain and bone.

Question 15

Standard Chemotherapy for SCLC

Answer 15

Etoposide + Cisplatin or Carboplatin

Question 16

Standard Treatment for NSCLC

Answer 16

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.

Question 17

Pemetrexed

Answer 17

Methotrexate analog (DHFR inhibitor). Maintainance dosing given for patients with stable or responding disease following 4 cycles of nonpemetrexed-platinium combination therapy.

Question 18

MOA of Carboplatin, Cisplatin

Answer 18

Forms DNA inter strand cross links and adducts

Question 19

MOA of Cyclophosphamide

Answer 19

Pro-drug of active alkylating moiety

Question 20

MOA if Docetaxel

Answer 20

Microtubule stabilizer inhibiting depolymerization

Question 21

MOA of Doxorubicin.

Answer 21

Intercalator, free radical generator, topo II inhibitor

Question 22

MOA of Etoposide, VP-16

Answer 22

DNA-topo II complex stabilizer

Question 23

MOA of Gemcitabine

Answer 23

DNA polymerase inhibitorvia incorporation of triphosphate form during DNA synthesis

Question 24

MOA of Ifosfamide

Answer 24

Intra and Inter strand crosslinker

Question 25

MOA of Irinotecan

Answer 25

DNA-topo I complex stabilizer

Question 26

MOA of Paclitaxel

Answer 26

Microtubule stabilizer inhibiting depolymerization

Question 27

MOA of Pemetrexed

Answer 27

DHFR inhibitor

Question 28

MOA of Topotecan

Answer 28

DNA topo I complex stabilizer

Question 29

MOA of Vincristine, Vinorelbine

Answer 29

Microtubule inhibitor; Tubules disintegrate into spiral aggregates/ protofilaments

Question 30

Cisplatin Toxicities

Answer 30

Nephrotoxicty, Ototoxicity.

Question 31

Cyclophosphamide Toxicities

Answer 31

Hemorrhagic Cystitis

Question 32

Docetaxel Toxicities

Answer 32

Sensory Neuropathy

Question 33

Doxirubicin Toxicities

Answer 33

Cardiotoxicity in cummulative dose exposure.

Question 34

Etoposide Toxicities

Answer 34

Alopecia

Question 35

Vinca Alkaloid Toxicity

Answer 35

Neuropathic Toxicities

Question 36

Erlotinib

Answer 36

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

Question 37

Afatinib

Answer 37

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.

Question 38

What is a common side effect of EGFR/ TKI

Answer 38

Rash is common and is often used as proof for physicians that the drug has reached effective concentration levels.