Therapeutics of Oncology

Question 1

what normal cell populations do chemotherapy drugs target as they target ALL rapidly dividing cells?

Answer 1

guts, BM, and hair follicles

Question 2

a type of dosing that allows recovery of normal tissue between treatment intervals

Answer 2

fractionation

Question 3

adjunct to local therapy (targets microscopic dz after surgery)

Answer 3

adjuvant

Question 4

prior to definitive tx in an attempt to shrink tumor

Answer 4

neoadjuvant

Question 5

sole tx for measurable dz

Answer 5

induction/maintenance

Question 6

improve QOL by helping alleviate signs

Answer 6

palliative

Question 7

what are three things that are important to communicate to the client prior to administration of chemotherapy?

Answer 7

cost, potential toxicities, and logistical requirements

Question 8

T/F: chemotherapy drugs are dosed based on toxicity rather than efficacy

Answer 8

TRUE (MTD, administered at highest possible tolerable dose)

Question 9

what chemo drugs should you be careful in dosing for small dogs (increased risk when dose based on BSA)?

Answer 9

doxorubicin, melphalan, cis- & carboplatin (consider dosing in mg/kg instead)

Question 10

what are the “4 R’s” considered prior to any chemo tx?

Answer 10

right drug, right dose, right route, right patient

Question 11

_____ codes for the production of p-glycoprotein (Pgp) pumps, which act to remove drugs from individual cells

Answer 11

ABCB-1 gene (used to be MDR-1 gene)

Question 12

what drugs are substrates of the ABCB1 pump and are therefore an increased risk when used in animals with the mutation?

Answer 12

vincristine, vinblastine, paclitaxel, and doxorubicin (adjust dose 30-40%!!)

Question 13

what are three most popular breeds (among others) with the ABCB-1 gene mutation?

Answer 13

australian shepherd, collie, and long-haired whippet

Question 14

what are the common adverse events seen with chemotherapy?

Answer 14

BM suppression, alopecia (non-shedding breeds ONLY = poodles, old english sheep dogs, shih tzu’s & terriers), GI signs (v/d)

“BAG of SEs”

Question 15

what must you do the day of chemotherapy tx before administration?

Answer 15

CBC

Question 16

how many neutrophils and platelets are required in order to give chemotherapy?

Answer 16

neutrophils >3000/ul
platelets > 100,000/ul

too low? recheck CBC in 3-7 days

Question 17

expected low point of BM insult

Answer 17

NADIR, check CBC weekly to establish (typically 5-10 days…carboplatin = 7-14 d)

Question 18

at what point would you decrease your chemo drug by 20-25%?

Answer 18

neutrophils below 1500 or platelets below 60,000 at the nadir

Question 19

your patient on chemo is myelosuppressed (neutropenia of <1000). what prophylactic antibiotics might you consider?

Answer 19

clavamox & baytril, sulphadiazine-trimethoprim

Question 20

your myelosuppressed chemo patient has been given prophylactic antibiotics but is still in bad shape, what last resort treatment could you consider?

Answer 20

nupogen (filgastim)

human form = neutralizing Abs > ONE TIME USE

Question 21

how do you manage a chemo patient with thrombocytopenia (<25,000)?

Answer 21

exercise restriction, close monitoring for bleeding (nose, GI)

Question 22

what are some signs of nausea to look for (especially in really stoic animals) in chemo patients?

Answer 22

ptyalism, constant licking, packing, chewing and aggression/redirected aggression

Question 23

what two drugs are most known for causing GI toxicity in chemo patients?

Answer 23

cisplatin and doxorubicin

Question 24

what are the two major categories of drugs with cell-cycle specific MOA?

Answer 24

antimitotics (M phase > mitotic) and antimetabolites (S phase > DNA synthesis)

Question 25

what are the two major categories of drugs with cell-cycle nonspecific MOA?

Answer 25

alkylating agents and antibiotics

Question 26

name two antimitotic drugs used in chemotherapy?

Answer 26

vinca alkaloids (vincristine/vinblastine) and taxanes (paclitaxel and docetaxel)

Question 27

what is vincristine used for and what are the common clinical signs seen?

Answer 27

LSA & TVT GI, vesicant, ileus, neuropathy (usually dragging back legs)

Question 28

shit! you extravasated vincristine in your patient! what now?!

Answer 28

dry WARM compress 20-30 min q6 x 24-48 hrs disperse & dilute give hyaluronidase (separates tissue planes & aids in improving absorption of extravasated drug into circulation)

Question 29

chlorambucil, cyclosphosphamide, lomustine (CCNU), melphalan, dacarbazine and ifosamide are all what type of chemo drugs?

Answer 29

alkylating agents > bind DNA strands, insert alkyl group and change structure of DNA to interfere with transcription, replication & repair machinery

Question 30

what category of BAG do alkylating agents cause?

Answer 30

bone marrow suppression

Question 31

in addition to BM suppression and alopecia, what is a major side effect of cyclophosphamide?

Answer 31

sterile hemorrhagic cystitis (acrolein)

Question 32

in addition to BM suppression, what organ is affected most by lomustine (CCNU) and what can you give in addition to prevent the effects?

Answer 32

liver, give w/ denamarin (hepatoprotectant)

Question 33

name some common antibiotic agents used for chemotherapy

Answer 33

doxorubicin ("red death" = adriamycin), mitoxantrone ("blue thunder"), actinomycin-D, and idarubicin

Question 34

what are the common clinical signs seen when using doxorubicin?

Answer 34

GI, dose related cardiotoxicity (prescreen boxers/dobies), tinnitus and vesicant give w/ dexrazoxane (zinecard) = reduces cardiotoxicity

Question 35

T/F: doxorubicin is more cardio sparing than mitoxantrone

Answer 35

FALSE, opposite

Question 36

shit! you extravasated doxorubicin in your patient! what now?!

Answer 36

ICE!!! localize and neutralize

Question 37

covalent binding to DNA strands, forming interstrand crosslinks which is cytotoxic

Answer 37

platinum agents

Question 38

inhibits protein synthesis in cells by hydrolysis of L-asparginase to L-aspartic acid

Answer 38

l-asparaginase (elspar) hypersensitivity rxn > NO IV ADMIN.

Question 39

_____ = SPLATS CATS! do not use

Answer 39

cisplatin use for OSA in dogs (BM suppression, GI, and nephrotoxic SEs...vigorous diuresis)

Question 40

what is carboplatin (a cell-cycle phase-nonspecific chemo drug) typically used for?

Answer 40

OSA and other sarcomas (BM suppression and NO nephrotoxicity)

Question 41

what is the 1st FDA approved lymphoma treatment for dogs used as "RESCUE" therapy?

Answer 41

tanovea - CA1 inhibits proliferation of lymphocytes & LSA cell lines by inhibiting DNA synthesis

Question 42

revolves around concept of eliminating break period by giving low dose continuous chemotherapy

Answer 42

metronomic chemotherapy

Question 43

what are the three main MOA for metronomic chemotherapy?

Answer 43

antiangiogenesis, immunomodulation, and direct targeting

Question 44

how does MC antiangiogenesis work?

Answer 44

blockage of COX & circulating endothelial progenitor cells (CEP's) upregulation of endogenous angiogenesis inhibitor thrombospondin-1

Question 45

Treg's =

Answer 45

CD4 + CD25 + regulatory T cells INHIBIT immune response = suppression of host tumor surveillance...UPREGULATED BY CANCERS MC decreases

Question 46

formation/accumulation of ACROLEIN and 4-hydroxymetabolites (by-products of cyclophosphamide metabolism) in the urine

Answer 46

sterile hemorrhagic cystitis (unique SE of cyclophosphamide = alkylating agent commonly used in MC protocols)

Question 47

what is the incidence of sterile hemorrhagic cystitis in MC protocols involving cyclophosphamide?

Answer 47

7-32%

Question 48

how can you avoid sterile hemorrhagic cystitis in a patient given cyclophosphamide?

Answer 48

give in AM w/ free access to water to encourage urination as well as concurrent glucocorticoid or furosemide

Question 49

what type of chemotherapy agent is palladia?

Answer 49

FDA approved tyrosine kinase inhibitor (tyrosine kinase receptors involved in activation & signal transduction) blocks variety of receptor tyrosine kinases expressed on cell surface...acts as reversible competitive inhibitor of adenosine triphosphate binding

Question 50

what cancer is palladia approved for use in?

Answer 50

patnaik grade II or III, recurrent, cutaneous MCTs w/ or w/o regional LN involvement

Question 51

form of cancer tx that boosts body's natural defenses to fight cancer

Answer 51

immunotherapy (biologic therapy)

Question 52

what type of immunotherapy is more commonly used in vet med?

Answer 52

tumor vaccines

Question 53

first DNA-based vaccine for cancer in either animals or humans (FDA approved)

Answer 53

canine melanoma vaccine -uses human tyrosinase to generate immune response against protein on canine melanoma cells, labeled for dogs w/ stage II or III oral melanoma, used in conjunction with sx and/or RT

Question 54

listeria-based antigen delivery system > vaccine freeze-dried formulation of modified-live, attenuated Listeria strain that activates cytotoxic T cells (listeria strain expresses tumor-associated antigen = activated T cells directed to fight cancer cells)

Answer 54

pipeline (OSA) MST = 956 days vs. 423 days

Question 55

what alternative therapy has shown to significantly delay progression of abdominal metastases in dogs w/ splenic HSA?

Answer 55

coriolus versicolor mushroom (turkey tail) -contains PSP that causes cell-cycle arrest at G1/S checkpoint w/ alterations in apoptogenic & extracellular signaling proteins > reduction in proliferation and increase in apoptosis of cancer cells

Question 56

class-1 protected chinese medication shown to improve clotting and enhance platelet function

Answer 56

yunnan baiyao prolong survival times in dogs w/ HSA > dose & time dependent HSA cell death through initiation of caspase-mediated apoptosis

Question 57

early responding tissue (RT)

Answer 57

epithelial layers of skin or mucosa and bone marrow effects seen w/in weeks

Question 58

late responding tissue (RT)

Answer 58

nervous tissue and bone effects seen w/in months or years

Question 59

what are the "big 3" variables that dictate the response of tissue to radiation?

Answer 59

total dose, fraction size, and duration of treatment

Question 60

RT total dose divided into larger doses given over a shorter period of time

Answer 60

hypofractionated dosing (i.e. oral malignant melanoma treatment)

Question 61

what is the most common modality for teletherapy?

Answer 61

megavoltage (deep) used for abdominal or deep seated tumors, xrays from cobalt and linear accelerator (linac) produces electrons to tx superficial lesions even, predictable distribution & deep penetration

Question 62

what are the two types of 3D- CRT (conformal radiation therapy)

Answer 62

intensity-modulated RT (IMRT) > inability to conform tx volume to concave shapes stereotactic RT (SRT) > allows precision delivery over dose, high dose fractions

Question 63

RECIST (response evaluation criteria in solid tumors)

Answer 63

complete response (100% resolution), partial response (>30% reduction in size), progressive dz (>20% increase tumor size), stable dz (<30% reduction, <20% increase tumor size)