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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
Tamoxifen functions as a antagonist in breast tissue, but an agonist where?
Stimulates the proliferation of endometrial cells, causes thickening of the endometrium, and increases the risk for developing endometrial cancer
26
Tamoxifen AE?
Generally, hot flashes
27
What are the types of aromatase inhibitors?
I = steroidal, binds irreversibly at androgenic binding site II = nonsteroidal, binds reversibly at heme of enzyme
28
What is an type I aromatase inhibitor and how does it work?
Exemestane (Aromasin®) Changes A/B ring to be more electrophilic and allows covalent bonds to be formed w/ enzyme
29
Exemestane (Aromasin®) AE?
Hot flashes Higher risk of osteoporosis/fractures
30
What is an type II aromatase inhibitor and how does it work?
Anastrozole and letrozole Triazole molecule + 4 position Nitrogen makes contact w/ heme of aromatase
31
Anastrozole and letrozole AE?
Hot flashes + night sweats Higher risk of osteoporosis/fractures
32
What drug is a SERD and where are the antagonistic effects?
SERM = tamoxifen SERD = fulvestrant (Faslodex®) Antagonistic in all tissues, reducing the total number of receptors present
33
Structure info on fulvestrant (Faslodex®)?
Estradiol analog with a lipophilic side chain at the 7-position (5 fluorine groups at the end)
34
Fulvestrant (Faslodex®) formulation?
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)
35
What are the 4 classes used for prostate cancer?
GnRH agonist (downregulation of receptors) GnRH antagonist CYP17 inhibitors AR antagonists
36
What changes are made to GnRH to form GnRH agonists?
Changes to the AA residues at positions 6 and 10 that lead to increased receptor affinity and resistance to enzymatic degradation
37
GnRH agonist formulations?
Multiple injectable formulations and SC implants that provide coverage from one month to a year
38
Which GnRH agonist is biodegradable?
Goserelin (Zoladex®) is a biodegradable implant while other implants must be removed
39
GnRH agonist AE?
After about 1 week, decrease in LH and FSH with testosterone reaching castration levels (<50 ng/dL) Symptom flares + PC growth
40
Degarelix is a GnRH antagonist and what molecule are they?
Degarelix is a 10 AA peptide that contains 3 proteinogenic AA residues and 7 residues that are synthetic AA derivatives
41
How do GnRH antagonist compete against GnRH?
Competes directly with GnRH for the binding site on anterior pituitary gland where its binding inhibits release of LH and FSH
42
Degarelix formulation?
Degarelix is dosed SC and forms a depot for continuous delivery, making it suitable for once monthly dosing
43
Degarelix AE?
Castration levels are reached in 3 days, but dont experience flares like GnRH agonists
44
Relugolix (Orgovyx®) is another GnRH antagonist. What kind of molecule is it?
small molecule (non-peptide),
45
Relugolix (Orgovyx®) interactions?
Substrate of P-gp
46
DHT and testosterone metabolism, what CYP enzyme is involved?
CYP17 17 alpha hydroxylase on pregnenolone C17-20-lyase on 17 alpha hydroxypregnenolone
47
CYP17 inhibition can prevent synthesis of testosterone in _______ and _______
peripheral tissues and tumors
48
CYP17 Inhibitor should be taken with what?
co-administered with low-dose glucocorticoids (prednisone)
49
Abiraterone Acetate (Zytiga®) MOA? Interactions?
IRREVERSIBLE CYP17 inhibitor due to C16-C17 double bond Has acetate ester on C3 Strong inhibitor of CYP2D6
50
How do Non-steroidal anti-androgens (NSAAs) work?
Compete directly with DHT for the binding site on ARs and inhibit the activation of gene transcription targets
51
Bicalutamide (R/S)-enantiomer is first oxidized by CYP3A4 prior to conjugation and has an elimination t½ of one week
R
52
Bicalutamide (R/S)-enantiomer is directly glucuronidated and rapidly cleared
S
53
Bicalutamide At steady-state, the plasma concentrations of the R-enantiomer are ___-times higher than the S-enantiomer
100x
54
Active metabolite to Enzalutamide (Xtandi®)? Interactions?
M2 (t½ = 7.8–8.6 days) Strong inducer of CYP3A4, CYP2C9 and CYP2C19
55
Breast cancer epidemiology Whats most common and how deadly? Mutations?
Most common in females and 2nd in death behind lung 5-10% BRCA mutations
56
RF for breast cancer?
Age ≥50yo Endogenous estrogen exposure Thoracic radiation before 30
57
Who should get genetic counseling for BRCA1/2 gene?
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
What are some biomarker testing tools used for breast cancer? EX: Mammaprint
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
What are some screening tools done for breast cancer?
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
Early stage breast cancer HR+, LN-, HER- Which one gets adjuvant endocrine or chemo?
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
Early stage breast cancer HR+, LN-, HER+ Which one gets adjuvant endocrine or chemo?
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
Early stage breast cancer LN+ Which one gets adjuvant endocrine or chemo?
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
What is the standard "chemo" drugs for breast cancer?
Stage I or II Doxotaxel + Cyclo, then pacitaxel or docetaxel + cyclo
64
What are the endocrine therapies? AE?
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
How is HER+ defined as?
ICH3 or 2 + FISH
66
Metastatic breast cancer + CDK4/6 inhibitors
Given with HR+, HER- "ciclib" drugs; generally neutropenia + fatigue P = myelosuppression A = diarrhea, liver, VTE R = myelosuppression heart, liver
67
What is used w/ PIk3CA mutation? BRCA1/2?
Apelisib - PIk3CA "parib" for BRCA1/2
68
ADT therapy + prostate cancer, what is the goal testosterone level?
<50 after 1 month using GNRH agonists/antagonist
69
What are the GNRH agonists?
Goserelin (Zoladex®)   Leuprolide (Lupron®, Eligard®) Triptorelin (Trelstar®) Histrelin (Vantas®)  
70
Issues with GNRH agonists?
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
Bicalutamide, flutamide, nilutamide AE?
Dont use as monotherapy! Bicalutamide (QD) + Flutamide (TID) = diarrhea + hematuria Nilutamide (used w/ orchiectomy) = diarrhea, disulfiram, visual changes, pneumonia
72
Advantages of GNRH antagonists vs agonists?
Less CV issues, no tumor flares, faster drop in testosterone
73
GNRH agonists AE?
Tumor flares, edema, inj. site rxn = acute osteoporosis, CV issues, diabetes = chronic
74
What are the GNRH antagonists?
Degarelix (Firmagon) Relugolix (Orgovyx)
75
Degarelix (Firmagon) Relugolix (Orgovyx) Which one should be avoided w/ P-gp + CYP3A inducers?
Relugolix (Orgovyx)
76
How fast do GNRH agonists and antagonists work?
7 days for antagonists, 28 for agonists
77
What are the agents used for systemic therapy for metastatic, castration naive prostate cancer (mCSPC)?
Abiraterone Enzalutamide Apalutamide Docetaxel
78
Docetaxel AE?
Edema, neutropenia, diarrhea
79
What is used with docetaxel to prevent issues?
Given every 21 days w/ steroids Decadron for AE Prednisone to enhance androgen blockade and mitigate AE
80
How is abiraterone taken?
4x250mg tabs or 2x500ER tabs on an EMPTY stomach
81
Abiraterone AE?
Liver, BP, edema
82
Abiraterone is with what other med?
Prednisone to prevent adrenal insufficiency
83
Yonsa is confused w/ abiraterone, why?
Micronized version and decreases the effect w/ food, but it's taken with methylprednisolone
84
PSADT ≤10 months, what do you take?
Apalutamide, enzalutamide, darolutamide
85
mCRPC + no prior docetaxel/NHT taken, what do you do?
Abiraterone Enzalutamide Docetaxel
86
mCRPC + just docetaxel was taken, what do you do?
Abiraterone Enzalutamide Cabazitaxel
87
mCRPC + just NHT was taken, what do you do?
Docetaxel, sipulecel-T
88
mCRPC + docetaxel and NHT were taken, what do you do?
Cabazitaxel
89
Abiraterone Enzalutamide Apalutamide Darolutamide Which one inhibits androgen synthesis?
Abiraterone The rest inhibit androgen RECEPTOR
90
Abiraterone Enzalutamide Apalutamide Darolutamide Which one is taken with food?
Darolutamide
91
Abiraterone Enzalutamide Apalutamide Darolutamide Which one is a CYP3A4 substrate?
Abiraterone The rest are inducers
92
Abiraterone Enzalutamide Apalutamide Darolutamide Which one does NOT cross BBB?
Darolutamide The rest do
93
Significance of AR-V7?
Indicates resistance to Abiraterone and enzalutamide
94
Sipuleucel-T Pembrolizumab Indications for both?
Sip = minimally or asymptomatic mCPRC Pembrolizumab = MSI-H or dMMR
95
Sipuleucel-T Pembrolizumab AE = immune mediated toxicities?
Pembrolizumab
96
Sipuleucel-T Pembrolizumab AE = back/flank pain
Sipuleucel-T
97
Sipuleucel-T Pembrolizumab AE = small % of stroke
Sipuleucel-T
98
What is Radium-223 for?
Symptomatic bone METS
99
Cabazitaxel AE?
Significant neutropenia; take w/ growth factors
100
Purpose of Mitoxantrone for prostate cancer?
For palliation of symptoms, no improvements on patient are made; given w/ prednisone
101
Olaparib Rucaparib Which one is indicated for BRCA+ mCRPC?
Rucaparib Olaparib is for HRR gene mutation
102
Olaparib Rucaparib Which one is renally dosed?
Olaparib
103
Olaparib Rucaparib Which one AE is both diarrhea or constipation?
Rucaparib Olaparib is just diarrhea
104
Olaparib Rucaparib AE?
Anemia, thrombo, N/V, liver

IPT: Hem/Onc/Transplant (7 decks)

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