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125 Cards in this Set
- Front
- Back
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thrombocytopenia
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decrease in platelets
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leukocytopenia
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decrease in WBCs
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doubling time of Ca cells? of normal cells?
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50-80 days
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how many cells present when tumor is first palpable?
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10 to the 10
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skipper's log kill hypothesis
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chemo kills by first order kinetics so can only kill a set % of cells each round
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resistance via insufficient drug uptake by cell
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methotrexate
daunomycin |
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resistance via insufficient activation of drug
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6-mercaptopurine
5-Fu |
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resistance via increased inactivation
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arabinosyl cytosine
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resistance via increased concentration of target enzyme (gene amplification)
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methotrexate
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resistance via decreased requirement for a specific metabolic product
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L-asparaginase
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resistance via increased utilization of an alternative pathway (salvage)
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antimetabolites
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resistance via rapid repair of drug-induced lesions
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alkylating agents
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resistance via increased efflux of drug (p-glycoprotein pump, multi-drug resistance)
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natural products
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phase I trials
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toxicology
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phase II trials
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standard doses (find responsive Ca)
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phase III trials
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compare to standard therapy
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Gleevec
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for CML
inhibits oncogene |
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Avastin
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anti-angiogenesis
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how is mustargen given?
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IV b/c lots of vesicant activity
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Mustargen use
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Hodgkin's and other lymphomas
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melphalan is cool because?
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alkylating agent that can be given orally (b/c of phenyl ring)
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chlorambucil is cool because?
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lease toxic nitrogen mustard
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melphalan use
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multiple myeloma
ovarian and breast ca |
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chlorambucil use
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chronic lymphocytic leukemia
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cytoxan (cychophosphamide) is given?
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orally--must be metabolized
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toxicity of cylophosphamide
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bladder and bone marrow
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cylophosphamide use
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leukemia and lymphoma
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action of alkylating agents
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bind directly to DNA to prevent DNA unwinding, causes DNA breaks
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MESNA
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binds acrolein in bladder to prevent toxicity when getting cytoxan or ifosfamide
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ifosfamide
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isomer of cytoxan
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use of ifosfamide
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osteosarcoma
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drawback of ifosfamide?
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more bladder toxicity
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thiotepa
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alkylating agent
used for recurrent bladder cancer |
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busulfan (myleran)use
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CML
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toxicity of busulfan
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not much
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nitrosureas given
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orally, require in vivo activation
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streptozocin
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nitrosurea
used for pancreatic islet cell carcinoma |
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triazene use
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melanoma
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methotrexate is an analog of
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folic acid
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tetrahydrofolate necessary for
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1 carbon transfer reaction (synthesis of DNA)
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toxicity of methotrexate
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infection
GI hemorrhage glossitis stomatitis |
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uses of methotrexate
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choriocarcinoma
leukemia and lymphoma sarcoma psoriasis breast head and neck arthritis |
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if using high dose methotrexate, need what
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leucovorin resuce
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leucovorin action
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provides tetrahydrofolate to rescue cells when undergoing methotrexate therapy
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5-Fu's mechanism of action (via intermediates)
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1. forms 5-dUMP - inhibits thymidilate synthase
2. forms 5-FUTP - can be incorporated into RNA |
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5-Fu is an analog of
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uracil
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why cancer cells susceptible to 5-Fu
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cancer cells convert 5-Fu to 5-Fdump faster than normal cells do
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role of leavocorin with 5-Fu
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stabilizes thymidylate synthetase and 5-FduMP complex
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uses of 5-Fu
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breast, GI, head and neck
+leavovorin for colon |
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how 5-Fu given
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iv
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cytabarine/Ara-C analog of
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2' deoxycytidine
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action of cytabarine
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inhibits DNA polyermase and ribonucleoside diphosphate reducatase
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does cytabarine require metabolism
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yes-- by deoxycytidine kinase
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resistance to cytabarine
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usually from increased activation by cytidine deaminase
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use of cytabarine
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acute leukemia
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6-mercaptopurine analog of
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hypoxanthine
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does 6-mercaptopurine need to be activated
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yes
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6-mercaptopurine's mechanism of action
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inhibits purine nucleotide synthesis and metabolism
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use of 6-mercaptopurine
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acute leukemia
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how is 6-mercaptopurine given
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oral
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imuran's use
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immunosuppressive to prevent rejection
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imuran's structure
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like 6-mercaptopurine
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allopurinol is
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analog of hypoxanthine
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action of allopurinol
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inhibits xanthine oxidase (and so conversion of purines to uric acid)
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toxicity of allopurinol
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makes toxicities of purine analogs (6-mercaptopurine and imuran) worse
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action of Vincristine (oncovin) and vinblastine (velban)
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bind to tubulin to cause metaphase arrest (M phase specific)
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toxicity of vinblastine
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myelosuppression
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toxicity of vincristine
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peripheral neuropathy
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use of vincristine
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Hodgkin's, acute leukemia
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use of vinblastine
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testicular ca, neuroblastoma, lymphoma
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etoposide's action
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inhibits topoisomerase II (S and G2 phase)
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taxol's action
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prevents depolymerization of microtubules (M phase specific)
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use of Taxol
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ovarian and breast cancer
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toxicity of Taxol
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peripheral neuropathy
myelosuppression |
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excretion of natural products v. alkylating agents/antimetabolites
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natural products = liver (bile)
alkylating agents/antimetabolites = kidneys |
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mechanism of action of Actinomycin D
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intercalates b/w adjacent base pairs of DNA
inhibits DNA dependent RNA polymerase |
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cycle specificity of actinomycin D
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none
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use of actinomycin D
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Wilm's Tumor
rhabdomyosarcome choriocarcinoma testicular cancer |
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daunorubicin and adriamycin mechanism of action
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intercalation of DNA
produces O2 radiacals, which damage DNA |
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toxicity of adriamycin
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heart
red urine |
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use of adriamycin
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solid tumors and leukemia
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mitoxantrone
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like anthracylines but less cardiac toxicity
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bleomycin's mechanism of action
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causes oxidative release of bases and DNA strand breaks
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toxicity of bleomycin
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lung (pulmonary fibrosis)
hyperpigmentation of skin bone marrow sparing |
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use of bleomycin
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testicular cancer
squamous cell carcinomas lymphoma |
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mitomycin C mechanism
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metabolically activated to become alkylating agent
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use of mitomycin C
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gastric cancer
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prednisone's mechanism of action
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lympholytic
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use of prednisone
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lymphocytic leukemia and lymphoma
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mechanism of leuprolide
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blocks release of ganadotropin (LH)
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use of leuprolide
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prostate cancer
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use of flutamide
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prostate cancer
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mechanism of flutamide
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blocks androgen receptor
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toxicity of leuprolide
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hot flashes
loss of lipido causes initial disease flare sometimes |
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toxicity of flutamide
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diarrhea
liver toxicity |
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mechanism of proscar
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blocks 5 alpha reductase (and so conversion of testosterone to DHEA)
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side effect of aromatase inhibitors
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loss of bone density
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examestane use
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breast cancer
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mechanism of examestane
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blocks aromatase
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mechanims of progestins
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down-regulates estrogen
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toxicity of progestins
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menstrual bleeding
edema |
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use of progestin
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endometrial cancer
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use of somatostatin
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pancreatic islet cell tumor
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use of asparaginase
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lymphocytic leukemia
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toxicity of asparaginase
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hypersensitivity
liver and CNS *bone marrow spared* |
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cisplatin mechanism
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alkylating
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phase specificity of cisplatin
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none
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use of cisplatin
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testicles, head, neck, ovary, cervix, bladder, lung
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toxicity of cisplatin
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kidney
ototoxicity peripheral neuropathy |
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advantage of carboplatin
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like cisplatin but less renal toxicity
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mechanism of procarbazine
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denatures DNA
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use of procarbazine
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Hodgkin's, lymphomas, lung, brain
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how is procarbazine given
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oral
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mechanism of hydroxyurea
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blocks ribonucleotide disphosphate reductase (and so DNA synthesis)
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phase specificity of hydroxyurea
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S
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hydroxyurea antagonizes what
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5-FU
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use of hydroxyurea
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leukemia
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MOPP is
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mustargen (mecholerhamine)
oncovin (incristine) procarbazine prednisone |
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MOPP used for
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Hodgkin's
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BVP use?
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testicular cancer
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BVP composition
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bleomycin
vinblastine platinum |
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CMF use
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breast cancer
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CMF composition
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cyclophosphamide
methotrexate 5-FU |
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FAM use
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gastric cancer
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FAM composition
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fluorouracil
adriamycin mitomycin C |
