Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Oncology Boards > Chemo > Flashcards

Chemo Flashcards

1
Q

Amiloride is a___ and does what when combined doxorubicin chemotherapy? (Poon, JVIM 2019)

A
  • Potassium sparing diuretic, inhibits sodium-hydrogen exchangers (NHEs that may contributed to tumor acidosis (Warburg effect) - Dox + amiloride synergistic, induce early and late apoptosis, upregulate p53 pathway = up Bax, down Bcl-xL and Akt phosphorylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Rate of clinical cardiotoxicity in dogs getting Dox (JVIM 2019, Hallman) Overall, high risk and non-high risk

A

Overall 4% High-risk 15.4% Non-high-risk 3%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Factors associated with increased risk of clinical cardiotxicity in dogs getting dox (JVIM 2019, Hallman)

A

Higher cumulative dose, higher body weight, decreases in fractional shortening after 5 doses of DOX, development of VPCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Expression of which ABC transporters in B cell and T cell LSA are associated with chemoresistance? (Zandvliet Vet J 2015)

A

B cell: ABCB1 T cell: ABCG2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What was the rate of neutropenia and thrombocytopenia from vinc in dogs that were either hetero or homozygous for MDR1 mutation compared to wt/wt dogs? (Mealey JVIM 2008)

A

mutants; 75% neutropenia, 62.5% thrombocytopenia wt/wt 11.5% neut, 4% thrombo too few dogs to compare hetero vs. homozygotes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What doses of doxorubicin and vinc have been shown to cause increased tox in dogs heterozygous MDR1 mutations?

A

dox 22.5mg/m2 vinc 0.56mg/m2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What type of mutation is present in dogs with ABCB1-1delta mutations? (Mealey JAVMA 2008)

A

4 base pair deletion that results in a frame shift that generates several premature stop codons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What breeds have had their % of ABCB1 mutations updated since the Mealey JAVMA 2008 study?

A

English shepherd (0% in JAVMA, now 15%)

McNab (0% in JAVMA, now 30%)

Chinook (not reported in JAVMA, now 25%)

Mixd breed (11% in JAVMA, now 5%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What was the rate of PgP expression in cats with LSA? How did this affect survival or outcome? (Brenn VCO 2008)

A

14/63 (22%) for one Ab, 40/63 (63%) for other Ab

Neither predictive for remission duration or survival

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which anatomic form of LSA in dogs was shown to express higher MDR1 compared to multicentric LSA? (Culmsee Res Vet Sci 2004)

A

GI LSA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the MOA of methotrexate?

A

folate analog that inhibits dihydrofolate reductase –> depletes reduced folate pools needed for purine and thymidylate biosynthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does methotrexate enter the cell?

A

Via active transport via the reduced folate carrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the oral bioavailablility of methotrexate

A

High at low does but becomes variable as doses increase –> high doses given IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why can GI side effects be seen at lower doses of methotrexate that are not high enough to cause myelotox?

A

PK dominated by enterhepatic recycling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the primary way methotrexate is excreted?

A

Primarlying intact drug through renal secretion and excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What other anti-cancer drug can block toxicity and antitumor activity of methotrexate

A

L-spar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

T/F methotrexate does not distrubute into the CNS

A

False - modest distribution to CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When is the peak toxicity for methotrexate

A

5-7d, returns to baseline w/in 14d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How was intrathecal cytarabine and methotrexate tolerated in dogs? (Genoni VCO 2014)

A

Overall well, 1 dog had seizure during admin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why should caution be used in giving pregnant patients methotrexate?

A

Particular teratogenic (common amongst antimetabolites)

likely to develop anomalies of skull or distal limbs

spontaneous abortions if given during first trimester

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is 5-FU?

A

halogenated analog of uracil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does 5-FU enter the cell?

A

Facilitated transport system (shared by adenine, uracil and hypoxanthine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the active forms of 5-FU

A

mono-, di- and triphosphate forms of fluorouridine and fluorodeoxyuridine

fluorodeoxyuridine monophosphate = FdUMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the primary MOA of 5-FU

A

Primary: FdUMP inhibits thymidylate synthetase –> preents thymidylate formation –> thymineless state = toxic to actively dividing cells

Other metabolites of 5-FU can be incorporated into RNA (FUTP)

Effects DNA synthesis/integrity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How is 5-FU excreted

A

Undergos extensive metabolism by dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil and then to alpha-fluoro-beta-alanine, ammonia and CO2

90% metabolized; that + parent drug excreted primarily through biliary excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the primary tox of 5-FU to dogs?

A

Dose-dependent myelosuppression, GI tox and neurotox

**ingestion of topical can be toxic and fatal**

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Why can’t you give 5-FU to cats?

A

Severe CNS toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What was the RR for dogs with gross disease carcinomas treated with concurrent 5-FU + carbo? CR was noted in 3 dogs with what cancer? (Menard VCO 2018) **committee member**

A

RR in gross disease = 43%

3 dogs with intestinal adenocarcinoma had CR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What AEs ocurred in dogs treated with concurrent 5-FU + carbo for carcinoma? (Menard VCO 2018) **committee member**

A

myelosuppression in 14/24 dogs (thrombo more common than myelo)

ataxic episode in 1 dog (not sure if otitis or 5-FU neurotox)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Why should you use caution in giving a pregnant patient 5-FU

A

highly teratogenic - deficits of nervous system, palate and skeleton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How does cytarabine enter the cell?

A

actively transported by nuceloside transporters (hENT1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

After entering the cell, cytarabine is phosphorylated sequentially by ____

A

CdR kinase (ara-c –> ara-cmp)

dCMP kinase (aracmp –>aracdp)

nucleoside diphosphate (NDP) kinase (ara-cdp –> aractp)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the activated form of ara-c in the cell, and what is its moa?

A

ara-CTP

primary MOA: incorporated into DNA and terminates DNA chain elongation (varies with concentration and time)

other MOA: competitive inhibition of DNA polymerase alpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Ara-C is (water/lipid)-soluble

A

water - distributes rapidly into the total body water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What % of plasma levels of ara-c are achieved in the CSF at steady state

A

60%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

ara-c has its highest activity during what phase(s) of the cell cycle

A

s-phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

overexpression of ____ and ____ can antagonize ara-c mediate apoptosis

A

BCL2 and BCLX

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How is ara-c eliminated

A

metabolized by cytidine deaminase in the liver, plasma and peripheral tissues

excreted in urine as ara-U

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How does ara-c work synergistically with alkylators and platinums

A

ara-c inhibits DNA alkylation repair

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are the dlts of ara-c

A

usually myelosuppression, occasionally gi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are 6-thioguanine and zebularine? (Flesner BMC 2014) **committee**

A

6-thioguanine = antimetabolite (purine analog)

zebularine cytidine anaolg with demethylating actvity + orally bioavailable

used in lymphoid malignancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the MOA of 6-thioguanine and zebularine and what was found in vitro when lymphoid cells were treated with these? (Flesner BMC 2014) **committee member**

A

downregulateds DNA methyltransferase1 (DNMT1) through ubiquitin targeted degradation (5-azacytidine also works this way)

inv vitro each agent reduced DNMT1 and global DNA methylation + dose dependent decrease in cell survival (apoptosis primary mode of cell death)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is the MOA of gemcitabine

A

inhibits DNA synthesis:

  • potent inhibitor of ribonucleotide reductase (RNR) –> depletion of deoxyribonucleotide pools –> apoptosis
  • weak inhibitor of DNA polymerase
  • incorporation into DNA –> strand termination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

How does GEM enter the cell?

A

active transport via nucleoside transporters (HENT1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What is the oral bioavailability of GEM

A

oral dosing = low systemic exposure likely because of extensive first pass metabolism in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

how is GEM eliminated

A

degraded via deamination by cytidine deaminase (GEM –> dFdU) in liver, plasma and peripheral tissues

renal excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Dosing at what time in relation to RT causes the most prominent radiosensitizing effects of GEM

A

before RT by 24-60hrs

remember - horrible tox for dogs and cats treated with GEM + RT for head and neck carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is the DLT of GEM

A

heme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What was the MTD of GEM and what was the DLT? (Marconato JVIM 2015)?

A

900mg/m2 30min IV bolus

neutropenia DLT (no non-heme DLT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

After what time period was GEM undetectable in the urine of dogs? (Marconato JVIM 2015)

A

24hrs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What are the adenosine analogs that are used in human oncology and generally what is their moa?

A

Fludarabine, pentostatin, cladribine, clofarabine

all inhibit ribonucleotide reductase and decrease pools of deoxynucleotides needed for DNA synthesis

most also can be incorporated into DNA as a false nucleotide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

How does hydroxyurea enter the cell

A

passive diffusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

what is the MOA of hydroxyurea

A

inhibits RNR –> decreases deoxyribonucleotide pools needed for DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

hydroxyurea selectively kills _____ cells in ____ phase

A

rapidly proliferating; S phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

How is hydroxyurea distributed in the body?

A

distributes rapidly to well-perfused tissues, slowly enters CSF, readily enters breast milk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Which AEs from hydroxyurea are cats more susceptible to?

A

myelosuppressive effects and possibly methemoglobinemia at higher doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What are the AEs related to hydroxyurea? What can happen in dogs after chronic treatment?

A

GI, myelosuppression (including anemia), rarely pulm fibrosis

dogs after chronic can develop onycholysis (painful detachment of the nail from the quick)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

How is hydroxyurea eliminated

A

hepatic metabolism + urinary elimination of the parent compound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Pregnant cats treated at what dose of hydroxyurea can have what toxicity?

A

higher than recommended doses (100mg/kg/day) can have fetal tox

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What specific heme change has been found ain dogs treated with hydroxyurea? (Conrado Vet Clin Path 2017)

A

Mild anemia + macrocytosis w/o corresponding increase in polychromasia

MCV progressively increased with tx for MCT; highest value 100fL at 6mo, rapidly decreased after hydroxyurea d/c

take home: megaloblastic changes have been reported in multiple spp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is at the + end of the microtubule and what is its function?

A

GTP cap - stabalizes the microtubule and prevents its disassembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What do microtubule associated protins (MAPs) do?

A

destabilize microtubules by promoting hydrolysis of GTP into GDP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is the MOA of the vinca alkaloids?

A
  • bind to a distinct site on tubulin and inhibit microtubule assembly –> dirsuption of mitotic spindle apparatus –> metaphase arrest and cytotoxicity
  • also inhibits signaling at c-Jun-N-terminal kinase and cell surface TK –> activate apoptotic pathway (malignant and non-malignant
  • Inhibits BCL-2 and other anti-apoptotic proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

How do the vincas enter the cell?

A

Passive diffusion (liophilic drugs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

How are the vincas excreted

A

extensive hepatic metabolism + biliary excreetion of parent drug and metabolites

10-20% of parent drug and metabolites excreted in urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What are the primary mechanisms of drug resistance for the vincas?

A

innate or acquired MDR through ABC transporters (PgP, MDR-1, multidrug resistance protein (MRP1))

decreased expression of class III beta-tubulin –> increases rate of microtubule assembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Does VBL or VINC have a longer T1/2

A

Vinc - possibly reason for greater neurotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What are the differences in the toxicity profiles of Vinc and VBL

A

vinc less myelosuppressive than vbl, but vinc causes more peripheral neurotox and GI effects (ileus)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What’s the plan for vinca extravasations

A
  1. infuse 5-10ml saline around affected area (can add hyaluronidase 150U/1ml if you can get it)
  2. Warm compress
  3. Topical application of DMSO + flucinolone acetonide (synotic) + 10mg flunixin meglumine after each warm compress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What was outcome of platelet counts in dogs treated with vinc for LSA? (Campbell JSAP 2019

A

plt higher after tx + number of thrombocytopenic patients lower

okay to give vinc to dogs with lsa that are thrombocytopenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What is the major cytochrome p450 in dogs that metabolizes vbl? (Achanta VCO 2016)

A

CYP3A12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What was the ORR and TTP for dogs treated with vinorelbine for various cancers (most pulmonary carcinoma or HS) (Wouda JAVMA 2015)

A

2% CR, 11% PR, 43% SD

TTP 103d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

What was the MTD and DLTs for cats treated with vinorelbine (Pierro JVIM 2013)

A

MTD 11.5mg/m2 weekly

DLTs - neutropenia, vomiting and nephrotoxicity

others: anemia, weight loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Compared to the antimetabolites, how teratogenic are the vinca alkaloids?

A

Less than antimetabolites, but can still cause spontaneous abortion, stillbirth and malformations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Are Border Collies that are ABCB1 WT more likely to develop vinc-associated myelosuppression (VAM) (Lind AJVR 2013)

A

according to this study, yes

3/5 BC developed VAM and no other dogs (21) developed VAM

No causative mutation found in this study, but 8 SNPs found in BC ABCB1

76
Q

What was the effect of prophylactic maropitant (immediately after and for 4 days after) after treatment with either vinc or ctx? (Mason JSAP 2014)

A

No difference in AEs between those that had prophylactic maropitant and those that did not

overall AES: 69% of dogs getting vinc, 81% of dogs getting ctx

77
Q

What was given to beagles treated with vinc that prevented reduced GI motility and resulted in fewer clinical GI AEs? (Tsukamoto JVIM 2011)

A

Mosapride citrate - gastroprokinetic agent that acts as a selective 5HT₄ agonist

78
Q

How long after administration was vinc detectable in the urine of dogs treated for LSA or MCT? (Knobloch JVIM 2010)

A

3 days after tx

79
Q

How long after administration was vbl detectable in the urine of dogs treated for LSA or MCT? (Knobloch JVIM 2010)

A

7 days after treatment

80
Q

How long after administration was ctx detectable in the urine of dogs treated for LSA or MCT? (Knobloch JVIM 2010)​

A

immediately after cytoxan, median residue concentration = 398.2ug/l but non-detectable in subsequent days

81
Q

How long after administration was doxo detectable in the urine of dogs treated for LSA or MCT? (Knobloch JVIM 2010)​

A

21 days after treatment

82
Q

How long after administration were VBL and CTX detectable in the serum of dogs treated for LSA or MCT? (Knobloch JVIM 2010)

A

VBL: detected in 1/81 samples 7d post treatment

CTX detected in 2 samples 1-2d after oral admin

conclusion: low risk of handling blood samples 1wk post-chemo

83
Q

What is the MOA of paclitaxel (PTX) and docetaxel (DTX)

A

stabilize microtubules aginst depolymerization

also, inhibit angiogenesis and bcl-2

84
Q

What component of the microtubules do the taxanes bind with high affinity to

A

Beta-tubulin

85
Q

What are the two most imortant ABC transporters involved in taxan resistance?

A

MDR1 (ABCB1) and MDR3 (ABCB4)

86
Q

What is recommended when treating with paclitaxel?

A

Premeds - desamethasone, antihistamine H2 receptor antagonist (human recs)

87
Q

What causes the hypersensitivity reactions seen with paclitaxel and docetaxel

A

The drug vehicles used - cremophor EL (paclitaxel), polysorbate 80 (docetaxel)

88
Q

How are the taxanes excreted

A

rapid distribution, slow elimination

hepatic metabolism + biliary excretion primarily, 10% or less renally excreted

89
Q

What are the DLTs for the taxanes

A

Diarrhea and neutropenia (remember, also causes hypersensitivity)

90
Q

What was the rate of hypersensitivity when dogs were treated with IV or SQ excipient-free nanoparticulate formulation of paclitaxel? (Selting VCO 2018) **committee member**

A

No hypersensitivities, overall well tolerated but couldn’t determine MTD because varied across dogs treated

91
Q

What was the result of treating canine HSA cells with Paccal Vet (water-soluble micellar paclitaxel) (Reckelhoff VCO 2019)

A

Cell death in time and dose dependent manner

Significant increases in apoptosis; cell cycle arrest at G2/M phase

92
Q

What were the AEs reported in 9 cats treated with paclitaxel (80mg/m2 IV q21d) for 1-2 doses? (Kim JFMS 2015)

A

AEs in 5/9 cats

Grade 3-4 thrombocytopenia

Grade 3 GI

Grade 3 hypersensitivity

93
Q

What was the rate of hypersensitivity reactions, neutropenia and death due to sepsis in dogs treated with 165mg/m2 IV over 3-6hrs of paclitaxel? (Poirier JVIM 2004)

A

64% allergic reactions

24% grade 3-4 neutropenia

12% died from sepsis

94
Q

What is the MTD of docetaxel in cats? (JVIM 2011 Shiu)

A

2.25mg/kg

95
Q

What were the AEs associated with 2.25mg/kg paclitaxel given to cats

A

DLT = neutropenia, vomiting, fever

hypersensitivity uncommon and mild

96
Q

What were the recommended doses of dcetaxel and cyclosporine A for treatments in cats? (McEntee JVIM 2006)

A

MTD docetaxel 1.75mg/kg + 5mg/kg cyclosporine

able to achieve therapeutic plasma concentrations at lower doses when given with cyclosporine

97
Q

What was the DLT and rate of hypersensitivity in dogs treated with 1.65mg/kg docetaxel + 5mg/kg cyclosporine A? (McEntee AJVR 2006)

A

No hypersensitivity

DLT = GI

98
Q

What can you give less docetaxel to dogs when giving with cyclosporine and achieve similar plasma concentrations as with higher doses of docetaxel given by itself? (McEntee AJVR 2006)

A

Docetaxel = substrate for PgP and metabolized by CYP3A

Cyclosporine A modulates both PgP and CYP3A

Docetaxel or availability by itself ~20% but increases to almost 100% when given with cyclosporine

99
Q

What are epothilones and what cancer have they been used against in dogs? (Meier JVIM 2013)

A

Epothilone B (patupilone) = microtubule stabilizing agens

used in 20 dogs for LSA - MTD 2.76mg/m2, DLT = GI

100
Q

What was the MTD of IV cytoxan in cats? (Moore Vet J 2018)

A

480mg/m2

101
Q

What was the DLT of ctx for cats at the MTD found in the Moore Vet J 2018 paper

A

neutropenia

30% grade 3-4 at 480mg/m2

102
Q

What is the recommended dosage of ctx for cats treated with single agent cytoxan?

A

460mg/m2 q3wks

103
Q

What was the highest inadvertently administered dose of cytoxan that resulted in a complete recovery in dogs? What were the AEs? Finlay JAAHA 2017

A

1750mg = 2,303mg/m2 over 21 days

severe SHC, severe nonregenerative pancytopenia, murmur (anemia?)

104
Q

What was CT able to incorporate into the BSA formula that the standard formula used does not? (Girens JVIM 2019) **committee member**

A

length

105
Q

Was metronomic or pulse dose ctx more likely to cause SHC in dogs? What about GI or bone marrow? (Ekena VCO 2018)

A

SHC: metronomic

GI/bone marrow: pulse

106
Q

Elevated liver values were found in _____% of dogs treated with CCNU vs. _____% of dogs treated with CCNU + Denamarin (Skorupski JVIM 2011)

A

CCNU: 84%

CCNU + Denamarin: 68%

107
Q

How did the degree of changes in liver values compare b/w dogs treated with CCNU vs. those treated with CCNU + Denamarain? (Skorupski JVIM 2011)

A

CCNU alone = greater increases in ALT, AST, SLP and bilirubin + more likely to have treatment delay or discontinue treatment

108
Q

_____% of dogs treated with CCNU alone had grade 3-4 ALT elevation vs. ____% of dogs treated with CCNU + denamarin (Skorupski JVIM 2011)

A

CCNU alone: 60%

CCNU + Denamarin: 32%

109
Q

CTX at low doses decreased what in dogs with STS? (Burton JVIM 2011)

A

Tregs and blood vessel density

110
Q

CTX at 12.5mg/m2 caused a decrease in _____ in dogs with STS while CTX at 15mg/m2 caused a decrease in _____.

A

12.5mg/m2 = number of Tregs but not %Tregs or tumor microvessel density

15mg/m2 = both the number and percent of Treg as well as tumor MVD were significantly decreased over 28 days​

111
Q

What was the MTD for dogs treated with Idarubicin and what were the DLTs? (Vail JVIM 2012)

A

MTD in dogs > 15kg = 22mg/m2

DLT = heme - neutropenia and thrombocytopenia

112
Q

What is elsamitrucin (Fiocchi JVIM 2011)

A

Most potent topoisomerase II inhibitor available

113
Q

What was the MTD of elsaitrucin in dogs? What were the DLT? (Fiocchi JVIM 2011)

A

0.08mg/kg) IV weekly

DLT = cardiac arrest (at 0.09mg/kg) severe diarrhea and anorexia

In people reportedly doesn’t cause neutropenia or cardiotox

114
Q

In dogs treated with pamidronate for bone pain, how many had increased BUN/Creat and how many had improved pain control if treated for OSA?

A

1/33 had increased BUN/creat

4/9 improved pain control for OSA

115
Q

Reduction of ______ was found in the urine of dogs treated with pamidronate and _____ was shown with the primary tumor (Fan JVIM 2005)

A

N-telopeptide (Urine N-telopeptide (NTx) excretion = mostsensitive and specific marker of bone resorption in humans with bone metastases

enhanced bone mineral density of primary tumor

116
Q

What was the MTD for pegylated TNFα in dogs? What was the DLT? (Thamm Clin Cancer Res 2010)

A

MTD 26.7ug/kg

DLT = vascular leak and coagulopathy/hypotension

Most common AEs = fever, diarrhea and vomiting

117
Q

What limits the clinical utility of TNFα? (Thamm Clin Cancer Res 2010)

A

Short T1/2

pegylated TNFα has increased cirulating T1/2, dcreased immunogenicity –> decreased toxicity

Increased intratumor drug concentration

118
Q

What was the MTD and DLT for a combination protocol of carbo/TOC? (Wouda VCO 2018) **committee paper**

A

200 mg m-2 IV every 21 days and approximately 2.75 mg kg-1 PO EOD, respectively.

The dose-limiting toxicity was neutropenia.

119
Q

What were the primary toxicities of hylauronan-cisplatin nanoconjugate (HA-Pt) in dogs? (Cai AJVR 2016) **committee paper**

A

37% myelosuppression 12.5% cardiotox, elevated ALT

No dogs had nephrotox

conclusion: effective in tumor bearing dogs, but high AE profile

120
Q

What is satraplatin? (Selting JVIM 2011)

A

Oral platinum drug

121
Q

What is the MTD of satraplatin in dogs, what was the DLT? (Selting JVIM 2011)

A

MTD: 35mg/m2/day for 5d every 3-4 weeks

Myelosuppression = DLT

thrombocytopenia at d14, neutropenia at d19

122
Q

What was the effect of Palladia on thyroid function in dogs? (Harper VCO 2019)

A

No dogs had low TT4, but significantly higher TSH in TOC dogs at 6wks vs. baseline

123
Q

What was the MTD for doxorubicin + TOC in dogs? What was the DLT? (Pellin VCO 2017) **Committee member**

A

MTD: 25mg/m2 doxorubicin q21d + 2.75mg/kg palladia EOD

DLT = neutropenia

124
Q

What was the overall biologic response rate in cats treated with palladia for advanced neoplasia? what was the median duration of the response? (Harper JFMS 2017)

A

RR 57.1%

median duration: 90d

**no SCC cats had a response**

125
Q

What AEs were reported in cats with advanced neoplasia treated with TOC? (Harper JFMS 2017)

A

10/14 had AEs, most mild myelosuppression or GI

2 cats developed severe hepatotoxicity

126
Q

What heme changes were found in dogs treated with a combination of TOC + metronomic cytoxan? (Mitchell JVIM 2012)

A

Toc sig decreased # and % of T regs in blood

TOC + CTX had increased IFN gamma, and decreases in Tregs

127
Q

What was the result of combining Masitinib increased the sensitivity of what cancer cells to vinblastine? What about Gem?

A

Increased sensitivity of HS to VBL

Increased sensitivity of OSA and Mammary to Gem

128
Q

What was the % clincal benefit in dogs with AGASACA treated with Palladia (London VCO 2011)

A

28/32 (87.5%)

8PR, 20SD

129
Q

What was the CB of Palladia for dogs with OSA? (London VCO 211)

A

11/23 = 48%

1PR, 10SD

130
Q

What was the CB for dogs with thyroid carcinoma treated with Palladia? (London VCO 2011)

A

12/15 = 80%

4PR and 8SD

131
Q

What was the CB for dogs with head/neck cancer (SCC) treated with palladia? (London VCO 2011)

A

7/8 = 87.5%

1 CR, 5PR, 1 SD

132
Q

What was the CB for dogs with nasal carcinoma treated with Palladia? (London VCO 2011)

A

5/7 = 71%

1 CR, 4 SD

133
Q

What was the overal clinical benefit for Palladia in solid tumors in dogs and what was the dosing used? (London 2011 VCO)

A

clinical benefit in 74% of dogs

median 2.8mg/kg M, W, F

134
Q

What was the MTD for CCNU + TOC? What was the DLT? (Pan VCO 2014)

A

Toc: 2.75mg/kg EOD + 50mg/m2 CCNU q3wk

DLT = neutropenia

135
Q

Wha3t was the ORR and biologic response to CCNU + TOC (Pan VCO 2014)

A

ORR 38.4%

Biologic response 53.8%

136
Q

What was the MTD of vbl + toc for dogs with MTC? (Robat VCO 2011)

A

TOC: 3.25mg/kg EOD + VBL 1.6mg/m2 q2wks

>50% reduction in dose intensity for vbl

137
Q

What was the ORR for dogs with MCT treated with VBL + TOC? (Robat VCO 2011)

A

71% response rate (+ enhanced myelosuppression)

138
Q

What 2 doses of masitinib were compared in cats and what were the AEs noted? (Daly JVIM 2011)

A

50mg EOD or 50mg q24hrs

2 cats developed clinically relevant proteinuria (10%) - both in daily dosing

Neutropenia in 15% of cats (mix of treatment groups)

some GI and increased creat

139
Q

What does eBAT target? (Oh clin pharm 2018) **committee paper**

A

targets EGFR on cancer cells and urokinase plasminogen activator receptor on cancer cells + associated vasculature

140
Q

What was the rate of proteinuria in dogs with cancer?What were the rates of the three levels assessed? How many azotemic or hypertensive? (Prudic JSAP 2018)

A

Overall 51% proteinuric

15% overtly

36.7% borderline

48.3% non-proteinuric

none azotemic

30% hypertensive

141
Q

What was the ST for dogs with HSA treated with splenectomy + dox followed by e-bat in the phase 1/2 study? (Borgatti mol canc ther 2017)

**committee member**

A

Improved 6mo survival from <40% to >70%

6 long term survivors

142
Q

What are the three forms of asparaginase that are available?

A

E.coli

pegylated e. coli asparaginase

erwinia crysanthemi asparaginase

143
Q

What are the advantages and disadvantages of pegylated e. coli asparaginase

A

nonimmunogenic in 70% of patients that reacted to e. coli asparaginase, but retains only 50% of activity

144
Q

What is the MOA of L-spar

A

enzyme hyrolyzes L-asparagine and displaces NH3 to form L-aspartate –> depletes L-asparagine and impairs protein synthesis –> apoptosis in lymphocytes

145
Q

What can irreversibly inhibit the reaction of asparaginase –> aspartate?

A

5-diazo-4-oxo-l-norvaline

146
Q

What are the main resistance mechanisms to L-spar

A

Upregulation of asparagine synthase

downregulation of apoptotic pathways

production of neutralizing Abs (silent hypersensitivity) - anti-lspar abs in 30% after 1st use and 60% after 2nd use

147
Q

What is the rate of anyphlaxis to l-spar in dogs and cats

A

dogs: 4.2%
cats: 0%

148
Q

Why should you not use l-spar near the time of surgery?

A

L-spar decreases protein synthesis and can cause hypoalbuminemia

149
Q

What may drive panc secondary to L-spar?

A

impaired protein metabolism –> hypertriglyceridemia

150
Q

Which clotting factors are particularly affected by l-spar

A

decreased vitamin K dependent (2, 7, 9, 10) and decreased anticoagulant factor production (AT III)

151
Q

What are the known drug interactions of l-spar

A

blocks activity of methotrexate

increases sensitivity to vinc

152
Q

What is the ORR to L-spar in cats? (LeBlanc 2007)

A

30%

15% CR, 15% PR

153
Q

Was there a difference in the AEs or ORR between compounded and commercially available L-spar? (Thiman 2016)

A

Nope.

154
Q

Why must small molecule inhibitors be dosed more frequently than monoclonal ab

A

both require constant pathway inhibition to inhibit the tumorigenic effects - shorter t1/2 means need more frequent dosing (like small molecule inhibitors) vs. longer t1/2 can be dose more intermittently (mAbs)

155
Q

What are the two main tyrosine kinase treatment strategies in humans?

A
  1. mAbs - block ligand binding, induce receptor endocytosis and destrcution or induce immune mediate cellular lysis
  2. RTKIs - bind to the ATP binding pocket and prevent activation
156
Q

What does toceranib target?

A

it is a split kinase - binds multiple things

  • Kit (SCFR)
  • CSF-1 (macrophage colony stimulating factor)
  • VEGFR2
  • PDGFR
  • FGFR
  • Flt-3
  • Flk-2
157
Q

What c-kit mutations are most commonly found in canine MCT? What about Cats?

A

dog: internal tandem repeats at the juxtamembrane region (exon 11>12) and less commonly extracellularly (exon 8>exon 9)
cats: extracellularly exon 8

158
Q

what are the ckit mutations found in GISTs

A

deletions in the juxtamembrane region

159
Q

What is the lowest evaluated dose of TOC that was found to be efficacious? (Bernabe BMC 2013)

A

2.4mg/kg PO EOD

160
Q

What is the metabolism of TOC?

A

Long T1/2 - 31hrs

primarily biliary with 92% excreted in feces

enterohepatic circulation

161
Q

What is the rate of hypertension secondary to TOC? (Tjostheim JVIM 2016)

A

37%

162
Q

What is the rate of elevated LEs with TOC + pred? What resolved this? (Carlsten JVIM 2012)

A

80%; resolved w/ denamarin

163
Q

What does Imatinib target?

A

c-kit, BCR-ABL, Src, PDGFR

164
Q

What is the MOA of rapamycin

A

binds to FKBP-12 or FK506 and inhibits mTOR activity

Can trigger p53 independent apoptosis

decreases expression of cyclin d1

165
Q

Rapamycin may inhibit _____ with prolonged use but _____ alteration was not detected in dogs

A

AKT

166
Q

What is a unique AE associated with IM injection of rapamycin?

A

sterile abscesses

167
Q

What are the rapamycin analogs and what do they block specifically?

A

temsirolimus/everolimus

block TORC1

168
Q

What are the most popular viruses used in gene therapy?

A

adenoviruses

169
Q

_____ deleted adenoviruses only replicate in cells deficient in _____

A

E1b; p53

170
Q

______ is a mAb targeting VEGF

A

Bevicizumab

171
Q

NSAIDs that target COX2 have been shown to reduce ____ and ____ in TCC

A

FGF and VEGF

172
Q

What is the MOA of thalidomide?

A

binds E3 ligase cereblon –> ubiquitination and proteasomal degradation of proteins including Ikaros and Aiolos

inhibits FNF-alpha production and redcued VEGF

stimulates T cell response against tumor cells and NK cells

173
Q

What was the average metronomic CCNU dose and what differences in AEs were noted between MTD CNNU and metronomic CCNU? (Tripp 2011)

A

2.84mg/m2

higher rates of azotemia for metronomic (10%, progressive in 1%)
lower rates of hepatotoxicity in metronomic (14%) than MTD (30%)

174
Q

What are examples of HDAC inhibitors?

A

vorinostat, romidepsin, valproic acid

175
Q

What are bortezomib and carfilzomib? How do they work?

A

proteasome inhibitors

targets and inhibits the 26s proteasome (which destroys damaged or misfolded proteins) –> halts protein synthesis and triggers autophagy

176
Q

Traztuzimab binds _____

A

HER2

177
Q

What are the bifunctional calssical alkylators?

A

nitrosoureas, nitrogen mustards

178
Q

What are the monofunctional alkylators

A

procarb, dacarbazine, TMZ

179
Q

CTX is oxidized by ____

A

cytochrome p450

180
Q

What toxicity can be causes at the doses of CTX used for bone marrow transplant?

A

cardiac toxicity

181
Q

How is melphalan metabolized and excreted?

A

no active metabolism, all spontaneous decomp (hydrolysis)

30% excreted unchanged in the urine

182
Q

What is the unique mechanism of drug resistance to melphalan?

A

decreased uptake due to downregulation of leucine transporters

183
Q

What chemo drug has the highest rate of secondary hematopoietic malignancy?

A

melphalan

184
Q

CCNU is lipid or water soluble?

A

Lipid - enters cell by passive diffusion

185
Q

How is CCNU excreted?

A

urine

186
Q

What drug interactions are known for CCNU?

A

drugs that upregulate cytochrome p450 increase rate of clearance and decrease efficacy of CCNU - important for pheno (CNS LSA)

187
Q
A

Oncology Boards (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions