Oncology 2 Flashcards

1
Q

What is targeted drug therapy?

A

targeted cancer therapies block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression

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2
Q

What is personalized medicine?

A

development and use of targeted therapy specifically in individuals known to have the mutation

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3
Q

What is the impact of gonadal hormones on some cancers?

A

some cancer cell growth is stimulated by gonadal hormones
-breast cancers (test for E and P receptors)

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4
Q

What is the cornerstone of managing prostate cancer?

A

androgen deprivation

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5
Q

Which cancers are hormone treatments used in?

A

breast cancer
endometrial cancer
ovarian cancer
uterine sarcomas
prostate cancer

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6
Q

What are the hormonal treatments used for breast cancer?

A

tamoxifen
-oral SERM
anastrozole, exemestane, letrozole
-oral aromatase inhibitors
goserelin acetate
-SC GnRH agonist

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7
Q

What is the MOA of tamoxifen?

A

SERM
-E antagonist in breast tissue
-E agonist in endometrium
cancer cell proliferation is prevented

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8
Q

In which cancer settings is tamoxifen used?

A

adjuvant (curative) and metastatic (not curative) settings for hormone receptor (ER or PR) positive breast cancers
-also used for breast cancer in men
-also used in gynecological cancers
-also used in sarcomas

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9
Q

In which women is adjuvant tamoxifen used?

A

premenopausal women
-systematic overviews of RCTs evaluating the effects of adjuvant tamoxifen for early breast cancer have shown increases in 10 yr survival and DFS survival rates in pts receiving 20-40 mg daily for 1-5 yrs or longer

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10
Q

What is the evidence for tamoxifen dosages exceeding 20 mg daily?

A

no indication that dosages exceeding 20 mg daily were more effective

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11
Q

What is the dose for tamoxifen?

A

20 mg po once daily

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12
Q

What is the magnitude of benefit from extended tamoxifen therapy in women with lower-stage breast cancer?

A

because the risk for breast cancer recurrence following 5 yrs of therapy is low in pts with small tumors compared to those with large tumors, the magnitude of benefit derived from the extended therapy is expected to be lower in pts with lower-stage disease

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13
Q

When is tamoxifen used in the palliative setting for breast cancer?

A

palliative setting of metastatic breast cancer
-used in premenopausal women at 20 mg once daily

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14
Q

When are aromatase inhibitors used for breast cancer?

A

postmenopausal women with breast cancer
-consistently shown to improve outcomes vs tamoxifen

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15
Q

What are the side effects of tamoxifen?

A

flushing, hot flashes (take AM)
hypertension
skin rash
fluid retention
nausea (hs, gets better, metoclopramide)
mood changes
arthralgia, arthritis
vaginal dryness or discharge

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16
Q

What are the serious adverse effects of tamoxifen?

A

DVT, PE, stroke
uterine cancer
risked increased in women 50 yrs and older

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17
Q

How is tamoxifen metabolized to its active moiety?

A

metabolized to active moiety (endoxifen) via CYP 2D6

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18
Q

What are the drug interactions of tamoxifen?

A

2D6 inhibitors
-ex: bupropion, fluoxetine, paroxetine, quinidine
-decreased [ ] of active metabolite
anticoagulants
-potentiates bleed risk with warfarin
grapefruit juice
-inhibits 3A4 metabolism of tamoxifen = toxicity

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19
Q

What is the MOA of aromatase inhibitors?

A

potent and selective nonsteroidal aromatase inhibitor
-prevents conversion of androstenedione to estrone and conversion of testosterone to estradiol

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20
Q

In which cancer settings are aromatase inhibitors used?

A

postmenopausal women in both adjuvant and metastatic breast cancer settings
-treatment of choice for adjuvant hormonal therapy to lower risk of breast cancer recurrence in postmenopausal women with early stage HR+ breast cancer
-also used in gynecological cancers

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21
Q

True or false: there is a clinically meaningful difference between the aromatase inhibitors

A

false

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22
Q

What are the adverse effects of aromatase inhibitors?

A

hot flashes and flushing
hypertension
osteopenia and osteoporosis
weakness, arthralgia
fatigue
less risk for DVT than tamoxifen
nausea/vomiting

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23
Q

Describe the use of goserelin acetate for adjuvant breast.

A

ovarian function suppression for premenopausal women at high risk for a new breast primary with HR+ disease to combine with an aromatase inhibitor

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24
Q

Describe use of goserelin acetate for metastatic breast.

A

use as a bride to oophorectomy in premenopausal women

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25
Q

Which agent is used for women not at a high risk of breast cancer recurrence?

A

tamoxifen

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26
Q

What is the most commonly diagnosed cancer in men?

A

prostate cancer
-responsible for < 10% of cancer deaths
-incidence is strongly correlated with age

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27
Q

What are the symptoms of prostate cancer?

A

difficulty urinating
dribbling after finishing urinating
need to urinate often
pain and blood during urination
difficulty having or maintaining erection
unplanned wt loss and appetite
pain or stiffness in lower back, hips, pelvis

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28
Q

What are the risk factors for prostate cancer?

A

older age (65+)
African American > Caucasian
family history
obesity

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29
Q

What are the treatment options for prostate cancer?

A

watchful waiting
-no tx and physician monitors growth with blood tests, rectal exams, biopsies
radiation therapy
-external beam RT or internal RT (brachytherapy)
radical prostectomy
-surgery to remove the whole prostate gland
hormone therapy
chemotherapy

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30
Q

What are the hormonal treatment options for prostate cancer?

A

GnRH agonists
-leuprolide acetate (IM), goserelin acetate (SC), relugolix (oral)
GnRH antagonist
-degarelix (SC)
CYP17 inhibitor
-abiraterone (oral)
antiandrogens
-apalutamide, darolutamide, enzalutamide, bicalutamide (oral)

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31
Q

What is the cornerstone of prostate cancer therapy?

A

hormone therapy
-androgen deprivation therapy

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32
Q

What is the goal of hormonal therapy for prostate cancer?

A

reduce serum testosterone to castrate levels
-testosterone causes the prostate tumor to grow
-objective tumor response 80-90%
-duration of response is highly variable

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33
Q

What is the MOA of leuprolide and goserelin in prostate cancer?

A

down regulation of hypothalamus-pituitary axis
-reduce serum testosterone almost as much as bilateral orchiectomy

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34
Q

What is seen initially with leuprolide or goserelin in prostate cancer?

A

initial “flare” response
-coprescribe bicalutamide for initial 14-30 days

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35
Q

In which prostate cancer settings is leuprolide or goserelin used?

A

either as neo-adjuvant and/or adjuvant treatment with a maximum duration of 3 yrs
indefinitely in prostate cancer for metastatic setting

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36
Q

What is the MOA of degarelix in prostate cancer?

A

blocks receptors in pituitary decreasing secretion of LH and FSH = rapid decrease in testosterone production
-reduces testosterone level more rapidly than LHRH agonists

37
Q

What is the difference between degarelix and leuprolide/goserelin at the initiation of prostate cancer treatment?

A

degarelix does not have the initial flare
-no need for bicalutamide

38
Q

What are the adverse effects of androgen deprivation therapy?

A

urinary symptoms
gynecomastia
hot flashes
decreased libido
erectile dysfunction
fatigue, wt gain, loss of muscle mass
osteopenia and osteoporosis
MI, prolonged QT

39
Q

What is the indication for abiraterone?

A

metastatic castration-sensitive prostate cancer in combination with prednisone and ADT
-may continue until disease progression or unacceptable toxicity
metastatic castration-resistant prostate cancer in combination with prednisone

40
Q

What is the MOA of abiraterone?

A

selectively inhibits CYP17
-blocks androgen production in testes, adrenal glands and tumor
-decreases cortisol production which increases ACTH leading to accumulation of mineralocorticoids (HTN, hypokalemia, edema)

41
Q

Why does abiraterone need to be co-administered with prednisone?

A

to prevent compensatory rise in ACTH

42
Q

What is the MOA of androgen receptor blockers?

A

bicalutamide, flutamide:
-competitively inhibit androgen binding to receptor
enzalutamide and apalutamide:
-competitively inhibit androgen binding to receptor
-also inhibit nuclear translocation of the AR and inhibit AR-mediated binding to DNA

43
Q

What is the difference between the prefix, substem, and suffix in the nomenclature of mAbs?

A

prefix: random = gives unique name
substem: designate the target
suffix: for all mAbs = mab
*name = prefix + substem + suffix

44
Q

Differentiate the different substems for mAbs.

A

-ci(r)- : circulatory system
-li(m)- : immune system
-t(u)- : tumor
-os :bone

45
Q

Differentiate the source of the mAb based on the suffix.

A

-ximab: chimeric
-zumab: humanized
-mumab: fully human

46
Q

Differentiate humanized and chimeric mAbs.

A

humanized:
-small but critical parts of the CDR are from non-human sources but larger constant regions of the heavy and light chains are human-derived
-generally > 90% human sequence
chimeric:
-Fc part of the Ig molecule is of a human sequence
-generally > 65% human sequence

47
Q

What is the pro of a mAb being more similar to human sequence?

A

less likely it is to elicit an immune reaction (decrease infusion reactions)

48
Q

What are the targets of mAbs in cancer?

A

cell surface antigen:
-CD20
-EGFR
-HER2
plasma protein:
-VEGF

49
Q

What are the indications for mAbs in cancer?

A

hematological malignancies
solid tumors

50
Q

How are mAbs best administered?

A

mAbs are proteins, so generally best administered parenterally
-some IV (bevacizumab)
-some SC and IV (rituximab, daratumumab)

51
Q

Is it possible to co-administer more than one mAb?

A

it is possible although this should only be done in situations in which the combination has been demonstrated to have greater efficacy
-pertuzumab + trastuzumab in HER2+ breast cancer along with a taxane

52
Q

What is the most common type of reaction to IV-administered mAbs?

A

infusion reactions

53
Q

When do infusion reactions typically develop to mAbs?

A

within 30 min-2hrs after the initiation of drug infusion
-sx may be delayed for up to 24h
majority of rxns occur after the 1st or 2nd exposure to the agent

54
Q

What are the signs and symptoms of infusion reactions?

A

fever and/or shaking chills
flushing and/or itching
alterations in HR and BP
dyspnea or chest discomfort
back or abdominal pain
NVD
skin rashes

55
Q

What is the second most common type of non-Hodgkin lymphoma?

A

follicular lymphoma

56
Q

What is the typical response to therapy in follicular lymphoma?

A

the vast majority of pts treated for FL will have an initial response to therapy with 40-80% demonstrating a complete response
-however, conventional therapy for FL is not curative and most will develop progressive disease

57
Q

What is used in the treatment of relapsed or refractory FL?

A

anti-CD20 mAbs in combo with different chemo regimens
-numerous studies demonstrated superior response rates when rituximab was added to conventional chemotherapy

58
Q

Which anti-CD20 mAbs are used in relapsed or refractory FL?

A

rituximab or obinutuzumab

59
Q

What is the MOA of anti-CD20 mAbs?

A

complement-dependent cytotoxicity
antibody-dependent phagocytosis
direct cell death
antibody-dependent cellular cytotoxicity

60
Q

When is obinutuzumab used for indolent lymphomas?

A

when there is resistance to rituximab

61
Q

What is rituximab resistance?

A

failure to respond to, or progression during, any previous rituximab-containing regimen or progression within 6 months of the last rituximab dose

62
Q

Which mAb is a bifunctional antibody?

A

blinatumomab

63
Q

What is the MOA of blinatumomab?

A

binds to CD19 present on precursor B-cell ALL cells AND binds to CD3 on T cells
-potentially recruiting cytotoxic T cells to kill the ALL cells

64
Q

Which cancers see the overexpression, dysregulation, or mutations in members of the HER family?

A

colorectal
head and neck
small cell lung cancers
EGFR has become of one of the most popular cancer treatment targets

65
Q

What are examples of EGFR inhibitor mAbs?

A

cetuximab
panitumumab

66
Q

What is the MOA of EGFR mAbs?

A

inhibit dimerization
-stops proliferation, angiogenesis, metastasis, and inhibition of apoptosis

67
Q

What are the indications for cetuximab?

A

locally advanced unresectable or metastatic, non-mutated all RAS colorectal cancer as a single agent or in combo with irinotecan
-also combined with radiation in head and neck squamous cell cancer

68
Q

Which EGFR mAb is better for colon cancer?

A

it is not clear which drug is better

69
Q

What is the indication for panitumumab?

A

single agent or in combo with irinotecan for tx of pts with non-mutated RAS

70
Q

What is the main difference between cetuximab and panitumumab?

A

cetuximab is a chimeric mAb
panitumumab is a completely human mAb
-lower incidence of hypersensitivity rxns (no predmedication needed)

71
Q

What is the MOA of VEGF mAbs?

A

bind to and neutralize VEGF to decrease VEGF signaling in pts with malignancy

72
Q

What is an example of a VGEF mAb?

A

bevacizumab

73
Q

What are the indications for bevacizumab?

A

advanced colorectal
advanced ovarian and cervical
recurrent glioblastoma
combo with atezolizumab in advanced liver

74
Q

What are the adverse effects of bevacizumab?

A

hypertension
bleeding
cerebral and myocardial infarction
proteinuria

75
Q

What is a notable property of bevacizumab?

A

extremely long half-life of 17-21 days after IV infusion

76
Q

Which mAb has high affinity for VEGFR2?

A

ramucirumab

77
Q

What are the indications for ramucirumab?

A

advanced gastric cancer and gastroesophageal adenocarcinomas

78
Q

What are adverse effects of ramucirumab?

A

infusion reactions are common
hypertension
bleeding
diarrhea

79
Q

What is overexpressed in many breast cancers?

A

~ 20% of breast cancers overexpress HER2

80
Q

What criteria should be used to select patients for HER2-targeted agents?

A

either 3+ staining by IHC or evidence of HER2 gene amplification by FISH is a strong predictive factor for sensitivity to HER2-targeted agents

81
Q

What are the anti-HER2 mAbs?

A

trastuzumab
pertuzumab

82
Q

Differentiate the MOA of trastuzumab and pertuzumab.

A

trastuzumab blocks HER2 dimerization
pertuzumab blocks heterodimerization

83
Q

What is used for HER-2 positive breast cancer?

A

trastuzumab and pertuzumab

84
Q

What is an adverse effect of HER2 mAbs?

A

decreased LVEF

85
Q

What are antibody-drug conjugates?

A

mAbs can be used to deliver a drug or a toxin to a specific site, which may be especially useful for cell killing in cancer therapy
-drugs or toxins are typically attached to the Ig molecule using covalent binding to prevent premature dissociation before reaching the target cell

86
Q

What is an example of an ADC using trastuzumab?

A

trastuzumab emtansine (T-DM1)
-ADC composed of trastuzumab, a thioether linker, and the antimicrotubule agent DM1
-DM1 = cytotoxic (no chemo needed)

87
Q

What is the use of T-DM1?

A

early stage (adjuvant) and metastatic HER2+ breast cancer

88
Q

What is the MOA of T-DM1?

A

emtansine released in cell and inhibits microtubule polymerization

89
Q

What is an ADC that is used for advanced bladder cancer?

A

enforumab vedotin