Oncology deck Flashcards
cetuximab & panitumumab
- MoA
- uses
- contraindications
- monoclonal antibodies that function as EGFR inhibitors
- used in stage 4 colorectal cancer (WT KRAS) + head/neck cancer
**have to test patient for presence of KRAS gain-of-function mutation before you begin them on this therapy (presence of KRAS-activating mutation will make this therapy ineffective since KRAS is downstream of EGFR)
rituximab
- MoA
- uses
- contraindications
- monoclonal antibody that inhibits CD20 on B cell surface
- used for B cell lymphomas (non-hodgkin’s), CLL, ITP, and RA
**can cause reactivation of JC virus –> progressive multifocal leukoencephalopathy in patients
denosumab
- MoA
- uses
**basically functions the same way as endogenous osteoprotegrin!!
- binds to RANKL receptor on osteoblasts to prevent it from binding to RANK on osteoclasts –> no osteoclast activation
- used to decrease bone metastases in cancers that frequently invade skeleton (PBKTL=prostate, breast, kidney, thyroid, lung)
tamoxifen & raloxifen
- MoA
- uses (including patient population)
- adverse effects
-both classified as SERM’s (selective estrogen receptor modulators) due to differential effects, depending on the tissue
- both are antagonists in the breast + agonists in the bone; tamoxifen is also an agonist in the endometrium whereas raloxifen is an antagonist
- tamoxifen is used for ER+ and/or PR+ breast cancer, specifically in PRE-menopausal women
- raloxifen is used for osteoporosis (elderly females)
- tamoxifen increases risk of endometrial carcinoma
- both increase risk of thromboembolic events (estrogen is a pro-coagulant)
anastrozole & lansoprazole
- MoA
- uses (including patient population)
-peripheral aromatase inhibitors –> inhibit estrone formation
- used for ER+ and/or PR+ breast cancer in POST-menopausal patients (main source of estrogen is from peripheral aromatase)
- *use this instead of tamoxifen because of the similar efficacy in decreasing estrogen levels but has no risk of endometrial carcinoma like tamoxifen does
- CANNOT be used for pre-menopausal women because it is a COMPETITIVE antagonist of aromatase and the ovaries make such a large amount of aromatase enzyme that it will be able to easily outcompete the drug and continue synthesizing large amounts of estrogen from ovaries
trastuzumab (herceptin)
- MoA
- uses
- adverse effects
- monoclonal antibody that binds to HER2 tyrosine kinase receptors to inhibit growth of HER2+ breast cancer cells
- also helps induce antibody-mediated cytotoxicity of the cancer cells themselves
- main use=HER2+ breast cancer
- can also be used for gastric cancer
-main adverse effect=cardiotoxicity!
(heart-ceptin!)
vemurafenib
- MoA
- uses
-specifically used for V600E mutation in the BRAF proto-oncogene, which is present in a percentage of patients with metastatic melanoma
rasburicase
- MoA
- uses
- functions as a uricase/uric acid oxidase enzyme (not normally present in humans but present in bacteria) to oxidize uric acid to its more soluble form, allantoin, for excretion
- used for prevention & treatment of tumor lysis syndrome
imatinib
- MoA
- uses
- BCR:ABL fusion protein kinase inhibitor
- used for CML, which is associated with 9:22 chromosomal translocation –> BCR:ABL fusion protein production
ruxolitinib
- MoA
- uses
-JAK1/2 non-receptor tyrosine kinase inhibitor
- used for all forms of chronic myelogenous proliferative disorders since these are all caused by over-activation of JAK2 –> excessive STAT activation and translocation to nucleus
- *works on all EXCEPT for CML (no JAK1/2 mutation here)
cladribine (2-CDA)
- MoA
- uses
- side effects
- adenosine deaminase inhibitor –> causes buildup of adenosine, which is directly lymphotoxic + throws off nucleotide pool balance in B cells –> apoptosis
- also inhibits DNA polymerase and causes DNA strand breaks
- used in hairy cell leukemia (mature CD20+ B cell neoplasm)
- nephotoxicity and neurotoxicity
**essentially a medication that causes the same defect that SCID patients inherit, which is why they have no B or T cells
doxorubicin
- MoA (3)
- uses
- toxicity & prevention
MoA:
- inhibits topoisomerase II –> inability to replicate DNA and apoptosis
- generates free radicals that damage cancer cell DNA
- also can intercalate into DNA strands directly
Uses:
- solid tumors
- leukemias
- lymphomas
Toxicity:
- cardiotoxicity is the main side effect; leads to dilated cardiomyopathy
- *give dexrazoxane (iron chelating agent) to prevent this
vincristine and vinblastine
- MoA
- adverse effects
MoA:
-bind to beta tubulin subunits and prevent them from polymerizing into microtubules –> prevent separation of chromosomes in mitosis –> inability to replicate and cell death
Adverse effects:
- vincristine causes peripheral neuropathy (inhibition of the microtubules in neurons, preventing movement of intracellular organelles and neurotransmitter delivery)
- vinblastine BLASTS the bone marrow (myelosuppression)
paclitaxel (and other taxols besides vincristine & vinblastine)
- MoA
- uses
- adverse effects
MoA:
-binds to polymerized microtubules to inhibit their DISASSEMBLY –> arrests chromosomes in M phase of mitosis
Uses:
-ovarian and breast carcinoma
Adverse effects:
-besides the usual, it can cause hypersensitivity rxn
capecitabine
- MoA
- adverse effects
MoA:
- oral form of 5-FU (normally given IV); gets converted to 5-FU in the body
- same function
Adverse effects:
-Hand foot mouth syndrome (painful sores that arise and may be dose-limiting in some patients, depending on the level of severity)
cytarabine
- MoA
- uses
- adverse effects
MoA:
-pyrimidine analog –> inhibits DNA synthesis in S phase/DNA polymerase
uses:
-leukemias (AML) and lymphomas
adverse effects:
- myelosuppression
- pancytopenia
- megaloblastic anemia
methotrexate
- MoA
- side effects
MoA:
- folic acid analog that competitively inhibits dihydrofolate reductase enzyme that reduces folate –> DHP –> THP
- prevents formation of methionine and thymidine (dTMP)
side effects:
- significant myelosuppression (can be rescued with LEUCOVORIN)
- pulmonary fibrosis
- mucositis (i.e-mouth ulcers)
- hepatotoxicity
leucovorin
-MoA
MoA:
-exogenous version of methylated THF (N5-formyl THF) given to restore the lack of THF for methionine and thymidine synthesis in healthy cells
- this decreases side effects of methotrexate
- enhances the functioning of 5-FU by providing more THF to combine with thymidylate synthase enzyme (5-FU complexes these together to prevent them for being used for dTMP synthesis)
bleomycin
- MoA
- side effects
MoA:
- induces free radical formation –> breaks in DNA strands
- *G2 phase specific (i.e-functions after the DNA is already replicated)
side effects:
- pulmonary fibrosis is major
- skin hyper-pigmentation
dactinomycin (actinomycin D)
- MoA
- uses
MoA:
-intercalates into DNA
uses:
-childhood tumors
busulfan
- MoA
- uses
- side effects
MoA:
-alkylating agent that cross-links DNA
uses:
- CML
- *used to obliterate bone marrow before a bone marrow transplant
side effects:
- severe myelosuppression almost all the time (which is why it is used before BMT’s)
- pulmonary fibrosis
- hyperpigmentation
cyclophosphamide and ifosfamide
- MoA
- side effects
- coadministered drugs
MoA:
- nitrogen mustards that require bio-activation by the liver
- cross links DNA at N7 guanine residues
side effects:
**hemorrhagic cystitis
coadministered drugs:
- mesna or N acetylcysteine
- both have thiol groups that bind to toxic metabolites produced by these drugs –> prevent hemorrhagic cystitis and significant myelosuppression
nitrosureas
- MoA
- uses
- side effects
MoA:
- crosses BBB –> cross-links DNA in the CNS
- *requires bio-activation before it can cross
uses:
-CNS tumors, including GBM
side effects:
-CNS toxicity (convulsions, ataxia, dizziness)
cisplatin and carboplatin
- MoA
- side effects
- coadministered drugs
MoA:
-platinum-based compounds (+ charge) that are attracted to neutrophilic residues on DNA (- charge) –> intercalate and cross-link DNA
side effects:
- carboplatin causes significant myelosuppression
- *cisplatin causes ototoxicity, nephrotoxicity, and peripheral neuropathy/neurotoxicity
coadministered drugs:
- amifostine (functions as a free radical scavenger to decrease toxicity)
- a lot of hydration is recommended to dilute out the toxic metabolites of cisplatin to prevent nephrotoxicity
