PHARM_GICANCER Flashcards
what are the 2 anticancer drugs used to treat carcinoid tumors?
IFN-alpha
octreotide
what are the 2 anticancer agents used to treat GIST tumors?
imatinib
sunitinib
all pts with gastric cancer should be tested for what mutation?
HER-2 for trastuzumab
how does octreotide work in the treatment of GI carcinoid tumors?
acts at somatostatin receptors to inhibit the secretion of serotonin & other GI-pancreatic peptides, which results in increased intestinal absorption of water & electrolytes, decreased gastric acid secretions, and increased intestinal transit time
which class of drugs used to treat carcinoid tumors inhibits disease progression and provides symptom relief in 75% of pts?
TNF-alpha inhibitors (may be have greater antitumor activity than somatostatin analogs)
why don’t conventional cytotoxic chemotherapeutic agents work in GIST tumors?
due to P-gp overexpression
which drug is used as 1st line treatment of unresectable metastatic or recurrent GIST?
imatinib
what is the main mutation in GIST tumors?
KIT-mutant
how is sunitinib used to treat GIST tumors?
given to pts with unresectable dz who progress on higher dose imatinib
80% of liver cancer worldwide are associated with what 2 kinds of infections?
HBV & HCV
explain how TACE is used in liver cancer
Trans-catheter arterial chemoembolization
- doxorubicin is injected while hepatic arterial branch feeding tumor is occluded with an emboli agent
- selective catheterization spares normal tissue & minimizes dispersion of drug away from tumor site
Bevacizumab MOA
inhibits binding of VEGF to its receptor, resulting in inhibition of tumor vascularization
capecitabine MOA
oral pro-drug metabolized to 5-FU
cetuximab MOA
rh/mMAb-EGFR
Cisplatin MOA
forms DNA intrastrand crosslinks & adducts
Docetaxel MOA
microtubule stabilizer inhibiting depolymerization
erlotinib MOA
EGFR-TKI
Fluorouracil MOA
pyrimidine antimetabolite that inhibits thymidylate synthase & interferes w/ RNA synthesis & function. Also has some effects on DNA
Gemcitabine MOA
DNA polymerase inhibitor via incorporation of triphosphate form during DNA synthesis
imatinib MOA
oral TKI as adjuvant treatment following complete resection of Kit (CD117) positive GIST
IFN-alpha MOA
enzyme activation following cell surface receptor binding and tyrosine kinase activation
Mitomycin MOA
mono or bifunctional alkylating agent
octreotide MOA
somatostatin analog; reduces duodenal bicarbonate, amylase, reduces gastric acidity, inhibits gallbladder contractility & bile secretions, inhibits meal-induced increases in SMA & portal venous blood flow
Sorafenib MOA
oral multi-kinase inhibitor targeting serine/threonine & receptor tyrosine kinases in both tumor & vasculature.
Sunitinib MOA
inhibits >80 receptor tyrosine kinases including PDGFR, VEGFR, KIT, FLT3, CSR-1R, RET
Trastuzumab MOA
HER-2/neu ab; HER2 is downregulated, cyclin-dependent kinase inhibitor p27 accumulates, & cell cycle arrest occurs. Also inhibits the constitutive HER2 cleavage/shedding mediated by metalloproteases, which may correlate with the clinical activity
AEs of bevacizumab
Bleeding GI perforation wound dehiscence HTN hypersensitivity
capecitabine AEs
Dihydropyrimidine DH deficiency (familial pyrimidinemia) prevents metabolic activation. Contraindicated in renal dysfunction Adverse CV events Neurologic & hematologic toxicities Interacts with coumarin
AEs of cetuximab
cardiac arrest, respiratory arrest, and/or sudden death
- infusion rxns
- acneiform rash common (76-88%)
Cisplatin AEs
dose limiting nephrotoxicity
bone marrow suppression
hearing impairment (ototoxicity)
Platinum hypersensitivity
Docetaxel AEs
increased treatment realted mortality in NSCLC
Edema
Contraindicated in hepatic dz
neutropenia (dose-limiting tox.)
what is the dose-limiting toxicity of docetaxel?
neutropenia
AEs of erlotinib
GI toxicity (N/V, diarrhea) prolonged bleeding elevated LFTs ocular toxicities rarely ILD
what are the AEs of fluorouracil?
Severe hematological tox. including BM suppression
dihydropyrimidine dehydrogenase deficiency (familial pyrimidinemia) lead to enhanced neurotoxicity; enzyme necessary for degrading fluorouracil to an inactive compound
AEs of gemcitabine
BM suppression infection peripheral neuropathy arthralgia drowsiness fatigue N/V, diarrhea anorexia common (resolves in 2-3 days)
AEs of imatinib
GI toxicities common (N/V/C)
CHF
neurologic tox.
fluid retention & edema
what are the AEs of IFN-alpha?
Neuropsychiatric events including aggression, depression and suicide
Flu-like symptoms: fatigue fever, alaise, myalgia, arthralgia, chills, headache, weight loss
what are the AEs of irinotecan?
BM suppresssion Diarrhea asthenia fever pain weight loss
which drug may used in place of 5-FU to treat colorectal cancer?
capecitabine
which 2 targeted agents appear to improve outcomes in colorectal cancer, except in pts with KRAS mutations?
bevacizumab
cetuximab
what drug class is the 2nd line therapy for esophageal cancer?
taxanes
what are the AEs of mitomycin?
BM suppression
Thrombocytopenia
leukopenia
Hemolytic-Uremic Syndrome
what are the AEs of octreotide?
dose related diarrhea
what do you have to monitor with octreotide therapy?
serum glucose; b/c it inhibits insulin & glucagon
which TKI causes QT prolongation, thrombocytopenia and bleeding?
sunitinib
what are the AEs of sunitinib?
thrombocytopenia & bleeding
QT prolongation
sometimes fatal GI complications including GI perfs have occured rarely in pts with intraabdominal malignancies
what are the AEs of Trastuzumab?
LVEF dysfunction & cardiomyopathy
Severe infusion-related rxns including anaphylaxis, angioedema, & pulmonary toxicity; pulm. tox worse in pts w/ intrinsic lung dz (COPD, asthma, Respiratory insufficiency)
