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IPT: Hem/Onc/Transplant > Block 3 > Flashcards

Block 3 Flashcards

1
Q

Colorectal incidence and death rates?

A

4th most common, but 2nd most deadly

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2
Q

Who are at highest risk of colorectal cancer?

A

Black men

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3
Q

USPSTF screening age for Grade A + B for colorectal cancer?

A

A = ≥50

B = 45-49

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4
Q

EGFR, RAS, BRAF mutations

What do you need to know?

A

If there is a mutation with RAS, EGFR targeted drugs wont work

Sames goes with BRAF mutations, EGFR + RAS drugs wont work

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5
Q

Colorectal staging?

A

I = invades submucosa or muscularis

II = invades through muscularis + into pericolorectal tissue

III = involves lymph nodes

IV = metastasis present

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6
Q

When is radiation utilized for colorectal cancer?

A

For rectal only, the laser may penetrate other vital organs if you used it on the intestinal tract

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7
Q

When is surgery used for colon cancer? Chemo?

A

Surgery for I + II

Chemo for high risk II + III + IV

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8
Q

Chemo regimen for stage IV

A

5FU/Leucovorin

Leu + 5FU + Oxaliplatin

Leu + 5FU + Irinotecan

Leu + 5FU + Oxaliplatin + Irinotecan

Capetican + Oxaliplatin

+/- Bevacizumab, Panitumumab, Cetuximab

  • must be RAS wildtype and left-sided
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9
Q

Stage IV + dMMR/MSI-H, what do you give?

A

Pembro or Nivo +/- ipilimumab

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10
Q

Stage IV + RAS wild type?

A

Regorafenib or trifluridine + tipiracil ± bevacizumab

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11
Q

Stage IV + HER2 AND RAS wild type?

A

Trastuzumab + (pertuzumab or lapatinib) or fam-trastuzumab deruxtecan

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12
Q

Stage IV + BRAF mutation?

A

Encorafenib + (cetuximab or panitumumab)

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13
Q

______ is rate limiting enzyme in 5FU catabolism

A

DPD

Partial deficiency - reduce dose by 50%

Complete deficiency - reduce dose by 90%

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14
Q

___________ (drug name) dose reduction recommended for patients who are UGT1A1*28 homozygous

A

Irinotecan

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15
Q

Capecitabine AE?

A

Hand-Foot syndrome; use urea-based cream, avoid friction and extreme temperatures

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16
Q

Trifluridine + Tipiriacil AE?

A

Myelosuppression; dose adjust if they have ANC <0.5 or PLT <50

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17
Q

Regorafenib AE?

Special info?

A

Must take with low fat meal (<600 calories + <30% fat)
CYP3A4 substrate
BCRP inhibitor (careful w/ fluvastatin/atorvastatin)

Hand-foot syndrome, HTN, diarrhea

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18
Q

How is estrone and estradiol formed?

A

Estrone from androstenedione via CYP19 (aromatase)

Estradiol from testosterone via CYP19 (aromatase)

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19
Q

What kind of steroid is estrogen? (C18/19/21)

A

C18

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20
Q

What are aromatase inhibitors used for and who is a good candidate?

A

Block the synthesis of estrogens in the periphery, not so much on the ovaries (Good for postmenopausal women)

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21
Q

What class does Tamoxifen belong to and who is a good candidate?

A

Selective estrogen receptor modulator (SERM) functions by directly blocking the binding of estrogens to ER and is an option for premenopausal patients

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22
Q

Tamoxifen activity is due to what group?

A

Beta-aminoethyl ether; OCCN-C

C

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23
Q

Tamoxifen is (hydrophilic/lipophilic) and is (highly/not highly) protein bound with a (long/short) half life

A

Tamoxifen is highly lipophilic, which contributes to its high protein binding (>98%) and long terminal half-life (5 to 7 days)

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24
Q

Tamoxifen metabolism?

A

Poor CYP2D6 metabolizers + comcimant CYP2D6 inhibitor meds may not benefit from tamoxifen therapy

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25
Q

Tamoxifen functions as a antagonist in breast tissue, but an agonist where?

A

Stimulates the proliferation of endometrial cells, causes thickening of the endometrium, and increases the risk for developing endometrial cancer

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26
Q

Tamoxifen AE?

A

Generally, hot flashes

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27
Q

What are the types of aromatase inhibitors?

A

I = steroidal, binds irreversibly at androgenic binding site

II = nonsteroidal, binds reversibly at heme of enzyme

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28
Q

What is an type I aromatase inhibitor and how does it work?

A

Exemestane (Aromasin®)

Changes A/B ring to be more electrophilic and allows covalent bonds to be formed w/ enzyme

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29
Q

Exemestane (Aromasin®) AE?

A

Hot flashes

Higher risk of osteoporosis/fractures

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30
Q

What is an type II aromatase inhibitor and how does it work?

A

Anastrozole and letrozole

Triazole molecule + 4 position Nitrogen makes contact w/ heme of aromatase

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31
Q

Anastrozole and letrozole AE?

A

Hot flashes + night sweats

Higher risk of osteoporosis/fractures

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32
Q

What drug is a SERD and where are the antagonistic effects?

A

SERM = tamoxifen

SERD = fulvestrant (Faslodex®)

Antagonistic in all tissues, reducing the total number of receptors present

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33
Q

Structure info on fulvestrant (Faslodex®)?

A

Estradiol analog with a lipophilic side chain at the 7-position (5 fluorine groups at the end)

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34
Q

Fulvestrant (Faslodex®) formulation?

A

Super lipophilic, renders the drug quite insoluble once injected into muscle, which enables very slow dissolution and a long duration of action (once monthly dosing)

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35
Q

What are the 4 classes used for prostate cancer?

A

GnRH agonist (downregulation of receptors)
GnRH antagonist
CYP17 inhibitors
AR antagonists

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36
Q

What changes are made to GnRH to form GnRH agonists?

A

Changes to the AA residues at positions 6 and 10 that lead to increased receptor affinity and resistance to enzymatic degradation

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37
Q

GnRH agonist formulations?

A

Multiple injectable formulations and SC implants that provide coverage from one month to a year

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38
Q

Which GnRH agonist is biodegradable?

A

Goserelin (Zoladex®) is a biodegradable implant while other implants must be removed

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39
Q

GnRH agonist AE?

A

After about 1 week, decrease in LH and FSH with testosterone reaching castration levels (<50 ng/dL)

Symptom flares + PC growth

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40
Q

Degarelix is a GnRH antagonist and what molecule are they?

A

Degarelix is a 10 AA peptide that contains 3 proteinogenic AA residues and 7 residues that are synthetic AA derivatives

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41
Q

How do GnRH antagonist compete against GnRH?

A

Competes directly with GnRH for the binding site on anterior pituitary gland where its binding inhibits release of LH and FSH

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42
Q

Degarelix formulation?

A

Degarelix is dosed SC and forms a depot for continuous delivery, making it suitable for once monthly dosing

43
Q

Degarelix AE?

A

Castration levels are reached in 3 days, but dont experience flares like GnRH agonists

44
Q

Relugolix (Orgovyx®) is another GnRH antagonist. What kind of molecule is it?

A

small molecule (non-peptide),

45
Q

Relugolix (Orgovyx®) interactions?

A

Substrate of P-gp

46
Q

DHT and testosterone metabolism, what CYP enzyme is involved?

A

CYP17

17 alpha hydroxylase on pregnenolone

C17-20-lyase on 17 alpha hydroxypregnenolone

47
Q

CYP17 inhibition can prevent synthesis of testosterone in _______ and _______

A

peripheral tissues and tumors

48
Q

CYP17 Inhibitor should be taken with what?

A

co-administered with low-dose glucocorticoids (prednisone)

49
Q

Abiraterone Acetate (Zytiga®) MOA? Interactions?

A

IRREVERSIBLE CYP17 inhibitor due to C16-C17 double bond

Has acetate ester on C3

Strong inhibitor of CYP2D6

50
Q

How do Non-steroidal anti-androgens (NSAAs) work?

A

Compete directly with DHT for the binding site on ARs and inhibit the activation of gene transcription targets

51
Q

Bicalutamide

(R/S)-enantiomer is first oxidized by CYP3A4 prior to conjugation and has an elimination t½ of one week

A

R

52
Q

Bicalutamide

(R/S)-enantiomer is directly glucuronidated and rapidly cleared

A

S

53
Q

Bicalutamide

At steady-state, the plasma concentrations of the R-enantiomer are ___-times higher than the S-enantiomer

A

100x

54
Q

Active metabolite to Enzalutamide (Xtandi®)? Interactions?

A

M2 (t½ = 7.8–8.6 days)

Strong inducer of CYP3A4, CYP2C9 and CYP2C19

55
Q

Breast cancer epidemiology

Whats most common and how deadly?

Mutations?

A

Most common in females and 2nd in death behind lung

5-10% BRCA mutations

56
Q

RF for breast cancer?

A

Age ≥50yo

Endogenous estrogen exposure

Thoracic radiation before 30

57
Q

Who should get genetic counseling for BRCA1/2 gene?

A

To be done before genetic TESTING

FH of BRCA gene

First 2 degree relatives w/ breast cancer at age <50

Male relative w/ breast cancer

Ashkenazi Jewish decent

58
Q

What are some biomarker testing tools used for breast cancer? EX: Mammaprint

A

Mammaprint used for HR+, HER-, LN- (LN+ for ASCO guidelines)

NCCN recommends looking when tumor size >0.5cm

No biomarker test for HER+ or TNBC

59
Q

What are some screening tools done for breast cancer?

A

Breast self exam - not generally recommended, but breast self awareness is recommended

Clinical breast exam - only NCCN recommends it, age 25-39 is every 1-3yrs, ≥40 is every year

60
Q

Early stage breast cancer

HR+, LN-, HER-

Which one gets adjuvant endocrine or chemo?

A

First look at tumor size

≤0.5 = adj. endocrine therapy

> 5, then look at RS

Not done? Adj endo +/- chemo

<26 = adj endo

≥26 = adj endo +/- chemo

61
Q

Early stage breast cancer

HR+, LN-, HER+

Which one gets adjuvant endocrine or chemo?

A

First look at tumor size

≤0.5 AND pNO = Consider adj. endo, +/- chemo and trast

≤0.5 AND pN1mi = Adj. endo, +/- chemo and trast

> 0.5 = Adj. endo, +/- chemo and trast

62
Q

Early stage breast cancer

LN+

Which one gets adjuvant endocrine or chemo?

A

Dont worry about tumor sizing

If HER2+ and HR +, Adj. endo, +/- chemo and trast + pertuzumab

If HER2-, dont worry about trast + pertuzumab

If HR-, dont do endo nor trast + pertuzumab

63
Q

What is the standard “chemo” drugs for breast cancer?

A

Stage I or II

Doxotaxel + Cyclo, then pacitaxel

or docetaxel + cyclo

64
Q

What are the endocrine therapies? AE?

A

LNRH agonist - goserelin (hot flash, bone loss, inj site pain)

SERM - tamoxifen (hot flash, fatigue, VTE, vaginal dryness, CYP2D6 interactions)

Aromatase inhibitors (anastrozole/letrozole; nonsteroidal) + exemestane (steroidal) = osteoporosis, myalgia

65
Q

How is HER+ defined as?

A

ICH3 or 2 + FISH

66
Q

Metastatic breast cancer + CDK4/6 inhibitors

A

Given with HR+, HER-

“ciclib” drugs; generally neutropenia + fatigue

P = myelosuppression

A = diarrhea, liver, VTE

R = myelosuppression heart, liver

67
Q

What is used w/ PIk3CA mutation? BRCA1/2?

A

Apelisib - PIk3CA

“parib” for BRCA1/2

68
Q

ADT therapy + prostate cancer, what is the goal testosterone level?

A

<50 after 1 month using GNRH agonists/antagonist

69
Q

What are the GNRH agonists?

A

Goserelin (Zoladex®)
Leuprolide (Lupron®, Eligard®)
Triptorelin (Trelstar®)
Histrelin (Vantas®)

70
Q

Issues with GNRH agonists?

A

Increased bone pain + urinary symptoms; generally lasts for 2 weeks

Should use antiandrogen therapy prior to starting these GNRH agonists (Bicalutamide, flutamide, nilutamide) for 2-4 weeks max

71
Q

Bicalutamide, flutamide, nilutamide AE?

A

Dont use as monotherapy!

Bicalutamide (QD) + Flutamide (TID) = diarrhea + hematuria

Nilutamide (used w/ orchiectomy) = diarrhea, disulfiram, visual changes, pneumonia

72
Q

Advantages of GNRH antagonists vs agonists?

A

Less CV issues, no tumor flares, faster drop in testosterone

73
Q

GNRH agonists AE?

A

Tumor flares, edema, inj. site rxn = acute

osteoporosis, CV issues, diabetes = chronic

74
Q

What are the GNRH antagonists?

A

Degarelix (Firmagon)

Relugolix (Orgovyx)

75
Q

Degarelix (Firmagon)

Relugolix (Orgovyx)

Which one should be avoided w/ P-gp + CYP3A inducers?

A

Relugolix (Orgovyx)

76
Q

How fast do GNRH agonists and antagonists work?

A

7 days for antagonists, 28 for agonists

77
Q

What are the agents used for systemic therapy for metastatic, castration naive prostate cancer (mCSPC)?

A

Abiraterone
Enzalutamide
Apalutamide
Docetaxel

78
Q

Docetaxel AE?

A

Edema, neutropenia, diarrhea

79
Q

What is used with docetaxel to prevent issues?

A

Given every 21 days w/ steroids

Decadron for AE

Prednisone to enhance androgen blockade and mitigate AE

80
Q

How is abiraterone taken?

A

4x250mg tabs or 2x500ER tabs on an EMPTY stomach

81
Q

Abiraterone AE?

A

Liver, BP, edema

82
Q

Abiraterone is with what other med?

A

Prednisone to prevent adrenal insufficiency

83
Q

Yonsa is confused w/ abiraterone, why?

A

Micronized version and decreases the effect w/ food, but it’s taken with methylprednisolone

84
Q

PSADT ≤10 months, what do you take?

A

Apalutamide, enzalutamide, darolutamide

85
Q

mCRPC + no prior docetaxel/NHT taken, what do you do?

A

Abiraterone
Enzalutamide
Docetaxel

86
Q

mCRPC + just docetaxel was taken, what do you do?

A

Abiraterone
Enzalutamide

Cabazitaxel

87
Q

mCRPC + just NHT was taken, what do you do?

A

Docetaxel, sipulecel-T

88
Q

mCRPC + docetaxel and NHT were taken, what do you do?

A

Cabazitaxel

89
Q

Abiraterone
Enzalutamide
Apalutamide
Darolutamide

Which one inhibits androgen synthesis?

A

Abiraterone

The rest inhibit androgen RECEPTOR

90
Q

Abiraterone
Enzalutamide
Apalutamide
Darolutamide

Which one is taken with food?

A

Darolutamide

91
Q

Abiraterone
Enzalutamide
Apalutamide
Darolutamide

Which one is a CYP3A4 substrate?

A

Abiraterone

The rest are inducers

92
Q

Abiraterone
Enzalutamide
Apalutamide
Darolutamide

Which one does NOT cross BBB?

A

Darolutamide

The rest do

93
Q

Significance of AR-V7?

A

Indicates resistance to Abiraterone and enzalutamide

94
Q

Sipuleucel-T
Pembrolizumab

Indications for both?

A

Sip = minimally or asymptomatic mCPRC

Pembrolizumab = MSI-H or dMMR

95
Q

Sipuleucel-T
Pembrolizumab

AE = immune mediated toxicities?

A

Pembrolizumab

96
Q

Sipuleucel-T
Pembrolizumab

AE = back/flank pain

A

Sipuleucel-T

97
Q

Sipuleucel-T
Pembrolizumab

AE = small % of stroke

A

Sipuleucel-T

98
Q

What is Radium-223 for?

A

Symptomatic bone METS

99
Q

Cabazitaxel AE?

A

Significant neutropenia; take w/ growth factors

100
Q

Purpose of Mitoxantrone for prostate cancer?

A

For palliation of symptoms, no improvements on patient are made; given w/ prednisone

101
Q

Olaparib
Rucaparib

Which one is indicated for BRCA+ mCRPC?

A

Rucaparib

Olaparib is for HRR gene mutation

102
Q

Olaparib
Rucaparib

Which one is renally dosed?

A

Olaparib

103
Q

Olaparib
Rucaparib

Which one AE is both diarrhea or constipation?

A

Rucaparib

Olaparib is just diarrhea

104
Q

Olaparib
Rucaparib

AE?

A

Anemia, thrombo, N/V, liver

IPT: Hem/Onc/Transplant (7 decks)

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