Oncology Flashcards
Busulfan
MOA: Alkylating age–cross links DNA
Uses: CML. Also used to ablate patients bone marrow before bone marrow transplantation.
Toxicity: severe myelosuppression, pulmonary fibrosis, hyperpigmentation
Cyclophosphamide
MOA: Alkylating agent. covalently crosslinks (interstrand) DNA at guanine N-7; requires bioactivation by liver
Uses: solid tumors, leukemia, lymphomas, some brain cancers
Toxicity: myelosuppression, bladder toxicity (hemorrhagic cystitis), partially prevented with mesna (thiol group of mesna binds toxic metabolites)
Cisplatin
MOA: cross-links DNA
Uses: testicular, bladder, ovarian, and lung carcinomas
Toxicity: nephrotoxicity and acoustic nerve damage. Protect nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis
Carmustine
MOA: nitrosoureas Alkylating agent. Cross links DNA. Requires bioactivation. Crosses the BBB into CNS.
Uses: brain tumors
Toxicity: CNS toxicity (convulsions, dizziness, ataxia)
Topotecan
MOA: Topoisomerase I inhibitor–prevents DNA unwinding and replication
Uses: ovarian and small cell lung cancers
Toxicity: severe myelosuppression, diarrhea
Etoposide
MOA: Topoisomerase II inhibitor–prevents re-ligation of DNA after Double stranded breaks and increases DNA degradation
Uses: solid tumors (particularly testicular and small cell lung cancers), leukemias, lymphomas
Toxicity: myelosuppression, GI irritation, alopecia
Doxorubicin
MOA: generate free radicals. Intercalates in DNA leading to breaks in DNA and decreased replication.
Uses: solid tumors, leukemia, lymphomas
Toxicity: dilated cardiomyopathy, myelosuppression, alopecia. Dexrazoxane (iron chelating agent) used to prevent cardiotoxicity.
Bleomycin
MOA: induces free radical formation which causes breaks in DNA strands
Uses: testicular cancer, Hodgkin’s lymphoma
Toxicity: pulmonary fibrosis, skin reactions, alopecia, hypersensitivity reactions, mucositis
Dactinomycin
MOA: Intercalates in DNA
Uses: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma, germ cell tumors (childhood tumors)
Toxicity: myelosuppression
Methotrexate
MOA: frolic acid analog that Inhibits dihydrofolate reductase, which converts dihydrofolate to tetrahydrofolate in order to participate in pyrimidine biosynthesis. Decreases dTMP and thus decreases DNA and protein synthesis
Uses: 1. Cancers: leukemias, lymphomas, choriocarcinomas, sarcomas 2. Non-Neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD
Toxicity: myelosuppression (reversible with leucovorin-folinic acid-“rescue”, mucositis (painful mouth ulcers), teratogenic, macrovesicular fatty change in liver
5-fluorouracil
MOA: Pyrimidine analog bio activated to 5F-dUMP, which covalently complexes folic acid–this complex inhibits thymidylate synthase leading to decreased dTMP and decreased DNA and protein synthesis
Uses: colon cancer, pancreatic cancer, basal cell carcinoma (topical)
Toxicity: myelosuppression (which is not reversible with leucovorin), overdose: “rescue” with uridine. Photosensitivity
6-Mercaptopurine
MOA: Purine analog that leads to decreased de novo purine synthesis. Activated by HGPRT.
Uses: preventing organ rejection, RA. Leukemia, IBD
Toxicity: bone marrow, GI, liver. Metabolized by xanthine oxidase, thus have increases toxicity with allopurinol, which inhibits their metabolism
Paclitaxel
MOA: Taxane, anti-microtubule agent. Hyperstabilizes polymerized microtubules in M phase so that mitosis spindle cannot break down (anaphase cannot occur)
Uses: ovarian ca, breast ca
Toxicity: myelosuppression, hypersensitivity reaction, alopecia
Vinblastine
MOA: microtubule inhibitor. Vinca alkaloid, anti-microtubule agent. Binds B-tubulin and inhibits it’s polymerization into microtubules, thereby preventing mitotic spindle formation and M phase arrest
Uses: solid tumors, leukemias, and lymphomas
Toxicity: myelosuppression
Tamoxifen
MOA: Selective estrogen receptor modulator–non-steroidal ligand for the ER that competes with endogenous estradiol–evokes tissue specific effects. Antagonist in breast and agonist in gone.
Uses: breast ca treatment and prevention
Toxicity: menopausal symptoms, partial agonist in endometrium increases risk for endometrial cancer
Imatinib
MOA: tyrosine kinase inhibitor that binds to the ATP binding site of BCR-ABL and c-kit–> growth arrest and apoptosis
Uses: CML, GI stromal tumors
Toxicity: fluid retention
Trastuzimab
MOA: Anti-HER2 specificity–a tyrosine kinase inhibitor. Help skill breast cancer cells that over express HER2 through inhibition of HER2-initiated cellular signaling and antibody-dependent cytotoxicity
Uses: HER2 positive breast cancer and gastric cancer
Toxicity: cardio toxicity,
Bevacizumab
MOA: Anti-VEGF specificity–inhibits angiogenesis
Uses: solid tumors (colorectal cancer, renal cell carcinoma)
Toxicity: hemorrhage and impaired wound healing
Cytarabine
MOA: pyrimidine analog leading to inhibition of DNA polymerase
USES: leukemias, lymphomas
TOXICITY: leukopenia, thrombocytopenia, megaloblastic anemia.
Azathioprine
MOA: Purine analog that leads to decreased de novo purine synthesis. Activated by HGPRT.
Uses: preventing organ rejection, RA, SLE. Leukemia, IBD
Toxicity: bone marrow, GI, liver. Metabolized by xanthine oxidase, thus have increases toxicity with allopurinol, which inhibits their metabolism
6-thioguanine
MOA: Purine analog that leads to decreased de novo purine synthesis. Activated by HGPRT.
Uses: preventing organ rejection, RA. Leukemia, IBD
Toxicity: bone marrow, GI, liver. Metabolized by xanthine oxidase, thus have increases toxicity with allopurinol, which inhibits their metabolism
Daunorubicin
MOA: generate free radicals. Intercalates in DNA leading to breaks in DNA and decreased replication.
Uses: solid tumors, leukemia, lymphomas
Toxicity: dilated cardiomyopathy, myelosuppression, alopecia. Dexrazoxane (iron chelating agent) used to prevent cardiotoxicity.
Ifosfamide
MOA: Alkylating agent. Same as cyclophosphamide. covalently crosslinks (interstrand) DNA at guanine N-7; requires bioactivation by liver
Uses: solid tumors, leukemia, lymphomas, some brain cancers
Toxicity: myelosuppression, bladder toxicity (hemorrhagic cystitis), partially prevented with mesna (thiol group of mesna binds toxic metabolites)
Lomustine
MOA: nitrosoureas Alkylating agent. Cross links DNA. Requires bioactivation. Crosses the BBB into CNS.
Uses: brain tumors
Toxicity: CNS toxicity (convulsions, dizziness, ataxia)
Semustine
MOA: nitrosoureas Alkylating agent. Cross links DNA. Requires bioactivation. Crosses the BBB into CNS.
Uses: brain tumors
Toxicity: CNS toxicity (convulsions, dizziness, ataxia)
Streptozocin
MOA: nitrosoureas Alkylating agent. Cross links DNA. Requires bioactivation. Crosses the BBB into CNS.
Uses: brain tumors
Toxicity: CNS toxicity (convulsions, dizziness, ataxia)
Vincristine
MOA: microtubule inhibitor. Vinca alkaloid, anti-microtubule agent. Binds B-tubulin and inhibits it’s polymerization into microtubules, thereby preventing mitotic spindle formation and M phase arrest
Uses: solid tumors, leukemias, and lymphomas
Toxicity: neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
Carboplatin
MOA: cross-links DNA
Uses: testicular, bladder, ovarian, and lung carcinomas
Toxicity: nephrotoxicity and acoustic nerve damage. Protect nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis
Teniposide
MOA: Topoisomerase II inhibitor–prevents re-ligation of DNA after Double stranded breaks and increases DNA degradation
Uses: solid tumors (particularly testicular and small cell lung cancers), leukemias, lymphomas
Toxicity: myelosuppression, GI irritation, alopecia
Irinotecan
MOA: Topoisomerase I inhibitor–prevents DNA unwinding and replication
Uses: colon cancer
Toxicity: severe myelosuppression, diarrhea
Hydroxyurea
MOA: inhibits ribonucleotide reductase–>decreases DNA synthesis
USES: melanoma, CML, sickle cell disease (increases HbF)
TOXICITY: bone marrow suppression, GI upset
Prednisone
MOA: May trigger apoptosis. May even work on non dividing cells.
USES: most commonly used glucocorticoid in cancer chemo. Used in CLL, non-Hodgkin lymphoma, also as immunosuppressant
TOXICITY: Cushing like symptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis
Prednisolone
MOA: May trigger apoptosis. May even work on non dividing cells.
USES: most commonly used glucocorticoid in cancer chemo. Used in CLL, non-Hodgkin lymphoma, also as immunosuppressant
TOXICITY: Cushing like symptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis
Raloxifene
MOA: Selective estrogen receptor modulator–non-steroidal ligand for the ER that competes with endogenous estradiol–evokes tissue specific effects. Antagonist in breast and agonist in gone.
Uses: prevent osteoporosis
Toxicity: no increased risk of endometrial cancer because it is an estrogen receptor antagonist
Rituximab
MOA: monoclonal antibody against CD20, which is found on most B-cell neoplasms
USES: non-Hodgkin lymphoma, rheumatoid arthritis (with MTX), ITP
TOXICITY: increases risk of progressive multi focal leukoencephalopathy
Vemurafenib
MOA: small molecule inhibitor forms of the B-Raf kinase with the V600E mutation
USES: metastatic melanoma
Cladribine
MOA: antimetabolite. Purine analog–>multiple mechanisms (e.g. Inhibition of DNA polymerase, DNA strand breaks)
USES: hairy cell leukemia
TOXICITY: leukopenia, thrombocytopenia, megaloblastic anemia
Erlotinib
MOA: EGFR tyrosine kinase inhibitor
USES: non-small cell lung carcinoma
Toxicity: rash
Amifostine
Prophylactic measure used with cisplatin and carboplatin chemo. Free radical scavenger used to prevent nephrotoxicity.
