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96 Cards in this Set

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Cure of cancer requires 10^? to 10^ cells be killed?
it requires 10^10 to 10^12 cells be killed
In marrow transplantation, is a leukemia patient more likely to relapse if donor is an identical twin or matched sibling?
identical twin
Which type of tumors are antigenic?
chemically and virally induced tumors
What two disorders are associated with a high incidence of malignancy?
inherited immuno deficiency and immunosuppression
What are the 4 reasons that chemo therapy is curative of large tumors when used alone?
1) Large tumors have a high proportion of non-proliferating cells. 2) first order kinetics (constant proportion) it would take the same amount of drugs to kill 10^10 to 10^7 cells as it would to kill 10^7 to 10^4 Cells. 3) between doses, while waiting for GI and bone marrow recovery, cells would rise to previous levels/or higher level. 4) resistance
what are the 5 principles of chemotherapy?
1. Use combination; 2. Use drugs that show effectiveness against the tumor in question; 3. Use drugs that use different mechanism to avoid resistance; 4 use drugs that have different toxicities; hit tumors early and hit them with the highest maximal doses
Name 3 mechanisms of resistance
1. MDR (pumps drugs out of the plasma); 2. Gene amplification (overprod of an enzyme that confers resistance of cells to drugs); 3. Resistance to alkylating agents
Name the 2 types of alkylating related resistance
1. Glutathione can combine with alkylating agents and diminish their activity (see the drug as a toxin); 2. Glutathione transferases - enzymes that mediates glutathione conjugation to alkylating agents
None
In gene amplification, which is related to unstable resistance, homeneous staining regions or "double minutes"?
Double minutes, which code proteins to confer drug resistance to tumor cells
What drug combinations are used in Breast cancer?
CAF, CMF, AT(cyclophosphamide, doxorubicin[adriamycin] or methotrexate, 5-FU
Which drug combinations are used in colon cancer?
5-FU with leucovorin
Which two drug combinations are used in Hodgkin's disease?
MOPP - mustard, oncovin (vincristine), procarbazine, prednisone. ABVD - Adriaycin (Doxorubicin), bleomycin, vinblastine, dacarbazine
Which two drug combinations are used to treat testicular cancer?
BEP - bleomycin, etoposie, cisplatin. VIC - Vinblastine, ifosfamide, cisplatin
What is tumor lysis syndrome?
tumor lysis --> b/d of nucleic acid products to cause uric acid production and renal damage
What is the potential risk of using antimetabolites?
Pregnancy: teratogens, and spontaneous abortions during the first trimester
Name three drugs associated with heart toxicity
Doxorubicin, cyclophosphamide, and anthracyclines (antibiotics)
Which two drugs are associated with lung damage?
Bleomycin and BCNU
Which drug is associated with kidney damage?
Cisplatin
Which two drugs are associated with buring or bloody uring?
cyclophosphamide and ifosfamide
What can be used to avoid the burning or bloody urine seen with cyclophosphamide and ifosfamide
Mesna (a sulfhydryl)
Name three drugs that can lead to peripheral numbness.
cyclophosphamide, cisplatin and vincristine
None
What are the toxicities associated with cyclophosphamide.
urine (burning & bloody), heart, neuro: numb/tinglining/hearing
None
In terms of pharmacokinetics, what is special about cyclophosphamide?
It is a prodrug
What are the 3 mechanisms of nitrogen mustards?
1. Covalent bonding, 2. Crosslinking DNA, and 3. 7-nitrogen guanine rxn (most cytotoxic)
What can be used with ifosfamide to avoid bladder toxicity and psychosis?
MESNA
Name the 5 classes of Alkylating agents.
Nitrogen mustards, alkyl sulfonates, nitrosourease, triazenes, platinum based compounds
Name the 4 classes of antimetabolites
folic acid analogs, pyrimidine analogs, purine analogs, substitute urea
Name 5 classes of Natural products. (HINT: VETAC)
Vinca alkaloids, taxanes, epipophylotoxins, camptothecins, antibiotics
None
Name 3 of biological hormone chemo drugs
Tamoxifen, leuprolide, flutamide
None
What are the 2 platinum based drugs?
Cisplatin and carboplatin
Which drug can enter the CSF and cause psychosis?
Procarbazine
None
What is dacarbazine use in?
melanoma, Hodgkin's (AVBD), and sarcomas
What is procarbazine used to treat?
Hodgkins MOPP
What class of drug is used in brain tumors and why?
Nitrosoureas, becaues they are lipid soluble
What are the mechanisms of action for cisplatin?
covalently binds DNA bases, can cross link N-7 or -6 of guanine
In terms of toxicity what is the difference and similiarity between cisplatin and carboplatin?
Cisplatin: less myelosuppression, but more nephrotoxic, and nausea causing than Carboplatin.
None
Cisplatin is highly toxic: name 4 precautions for its use
1. Don't use with other nephrotoxic drugs, 2. Monitor Mg, K and Ca (renal toxicity), 3. maintain high urine flow (vigorous hydration), 4. Aggressive use of antimimetics,
None
What are the two major concerns with carboplatin use?
nephrotoxicity (but less than cisplatin) and myelosuppression (MAJOR) especially WBC suppression
What is methotrexate an analog of?
folic acid
what is 5-FU an analog of
dUMP
What is methotrexate's mechanism of action?
inhibition of DHFR enzyme --> depletion of folates
How do methotrexate and aspirin interact?
Aspirin displaces methotrexate from plasma proteins
None
What can reverse the actions of methotrexate?
Leucovorin
What are 3 unique toxicities associated with methotrexate?
renal tubule obstruction, pneumonitis, neurotox after intrathecal admin... liver?
None
What are 4 precautions used with methotrexate?
1. Lower dose with reduced GFR, 2. Hyrdrate pt, 3. Continuous plasma concentration monitoring, 4. Can cause ascites, so monitor liver
None
give the pharmacokinetics of 5-FU
(5-FU is a pyrimidine analog) first it undergoes conversion to F-dUMP --> which then competes for thymidylate synthase with dUMP (to dTMP) and reduce DNA synth
What should 5FU be used with to potentiate treatment of colon cancer
Leucovorin
What is an uncommon toxicity related to 5FU?
reversible cerebral toxicity
How is 5-FU metabolized?
liver
What do 5FU, methotrexate, and gemcitibine have in common?
they are all antimetabolite cancer drugs
What is 2,2-difluorodeoxycytidine?
the active metabolite of gemcitibine
Which type of cancer is Gemcitibine use to treat?
non-small cell lung cancer, bladder cancer, and pancreatic cancer
What are the3 mechanisms of gemcitibine (dfdCTP)?
(1) competes with dCTP as DNA pol inhibitor... (2) inhibition of ribonucleotide reductase... and (3) it's incorportated into DNA leading to strand termination --> apoptosis
None
How would you describe the toxicities of Gemcitibine?
mild
What mechanism do vincristine and vinblastine share in common?
The both bind tubulin of the mitotic spindle and induce metaphase arrest
of vincristine and vinblastine, which causes myelosuppression?
vinblastine causes myelosuppression
of vincristine and vinblastine, which causes peripheral neuropathy?
vincristine
What are the 2 vinca alkaloids?
vincristine and vinblastine
What are the 2 taxanes?
Taxol and taxotere
Between taxol and taxotere, which is retained longer?
Taxotere
None
What is the mechanism of action of taxanes, and which other cancer drug is similar?
Taxanes bind tubulin like the vinca alkaloids, but it's not at the same site… taxanes renders the microtubules less suseptible to depolymerization (increasing microtubule level in cell)... also they may effect p53 dependent and independent apoptosis
None
What is the mechanism of resistance for taxanes?
related to p-glycoproteins --> and mutations in ∂ and ß subunits of tubulin
What are taxanes dissolved in to increase solubility?
cremophor E1 + EtOH
How is the anaphylactic rxn dealt with when using taxanes?
premedicate with antihistamines
Which are taxanes use to treat?
ovarian (with carboplatin), non-small cell lung cancer, breast cancer, prostate cancer
Compare the toxicities of taxol and taxotere.
taxol neuro toxicity >> taxotere… Taxotere cap leak syndrome>>> taxol… both can cause sensory neuropathy
what type of myelosuppression is seen in taxol and taxotere?
neutropenia and thrombocytopenia
What type of toxicity is seen in antibiotics (anthracyclines)?
cardiotoxicity
What is used to treat Wilm's tumor (a kidney tumor in children)
Actinomycin D (an antibiotic)
What is the mechanism of action for daunomycin and Doxorubican (both antibiotics)?
inhibits function of topoisomerase II (which serves to unwind DNA) causing DNA damage… but to a lesser degree it superoxide --> hydrogen peroxide
How is Daunomycina dn doxorubican eliminated?
liver
What type of toxicity is seen in daunomycin and doxorubicin?
cardiac toxicity due to a lack of catalase
How is at risk for toxicity in theuse of daunomycin and doxorubicin?
people w/ 1) HTN, 2) heart disease, 3) people receiving > 2,000 rads, 4) people that receive extravasation across a joint
What do actinomycin D, doxorubicin, bleomycin, etopiside (VP-16), and camptothecins, have in common?
they're all antibiotics used in treating cancer
What diseases are combinations are bleomycin used to treat?
AVBD (Hodgkin's) and BEP (testicular cancer)
what is the mechanism of action for bleomycin?
nicks DNA, inhibits DNA ligase, leading to the progresive DNA fragmentation
How can you tell if pulmonary toxicity is being caused by bleomycin?
drop in DL-CO2
How does Etopiside work?
in cancer, it acts by targeting topoisomerase II: relaxes DNA by generating transient single strand nicks
None
Which drugs inhibit topoisomerase I and II?
I: Camptothecins (irinotecan) … II: Daunomycin & doxorubicin… etopiside
None
What do toptecans and irinotecans have in common?
they are both camptothecins
Which prodrug must be converted to the active metabolite SN38?
Irinotecans
What is topotecan use to treat?
ovarian and lung cancer
What is irinotecans use to treat?
GI/colon cancer
Which patients respond well to tamoxifen?
Postmenopausal female responders had progesterone and estrogen receptors
What is the indication when a patient has bone pain and hypercalcemia in response to tamoxifen?
this indicates metastasis improvement
What are the SE of tamoxifen use?
hotflashes, increased endometrial cancer, venous thrombosis, anovulation, and problems with EYES!!! CATARACTS
None
What is the mechanism of action for tamoxifen?
blocks estrogen stimulation, and progesterone receptor synthesis and stimulates TGFß production
What is flutamide used to treat?
Flutamide is a antiandrogen used to treat prostate cancer
How does flutamide work?
it blocks cytoplasmic receptors of dihydrotestosterone
What is the toxicity associated with flutamide?
liver
What is leuprolide used to treat?
prostate cancer
How does leuprolide work?
leuprolide is an analog of GnRH, thus prevent its release--> producing surges in LH and FSH --> followed by their reduction --> followed by a fall in testosterone and dihydrotestosterone
What is the mechanism behind giving enzymes such as arginase?
some tumors cannot produce arginase, thus by reducing circulating levels of arginase the tumor cells are denied a necessary amino acid
What do isotretinoin and all trans retinoic acid do?
induce differentiation
name the Hematopoietic growth factors used in cancer treatment
erythropoietin, GM-CSF, and G-CSF
what toxicity is associated with the use of GnRH and LHRH analogs, such as leuprolide?
hot flashes, loss of libido, impotence