Therapeutics V Exam 2- Basic Oncology Iii

Front 1

steroids: anti estrogens for breast cancer (3 classes)

Back 1

SERM (typically start on this)
aromatase inhibitors
estrogen antagonists

Front 2

SERM MoA (2)

Back 2

competitive inhibitor of estrogen binding
to estrogen receptor, technically a selective
estrogen response modulator (SERM)
– partial agonist of the estrogen receptor

Front 3

2 SERMs

Back 3

tamoxifen
raloxifene

Front 4

AE of SERMs (4) has to do with where it acts as a estrogen agonist/antagonist

Back 4

N/V, hot flashes, DVT, increased risk of endometrial cancer

Front 5

raloxifene primary usage and benefit

Back 5

no established role in BC, indicated for the treatment and prevention of osteoporosis in postmenopausal women,

decreased risk of invasive breast
cancer in postmenopausal women with osteoporosis.

Front 6

aromatase inhibitor MoA

Back 6

Inhibit the final enzyme in the estrogen production pathway

Front 7

3 AE of aromatase inhibitors

Back 7

Arthralgias, myalgias, hot flashes

Front 8

non steroidal aromatase inhibitor
steroidal aromatase inhibitor

Back 8

anastrazole (non steroidal)

exemestane (steroidal)

Front 9

2 Mechanisms for estrogen antagonists

Back 9

Block all estrogen receptors, down-regulate & degrade ER

Front 10

AE of estrogen antagonists

Back 10

arthralgia, myalgia, hot flashes

Front 11

example of estrogen antagonist

Back 11

fulvestrant

Front 12

antiandrogen MoA

Back 12

Block androgen binding

Front 13

3 antiandrogens

Back 13

flutamide
bicalutamide
nilutamide

LUTAMIDE

Front 14

4 AE of antiandrogens (lutamides)

Back 14

Gynecomastia, sexual dysfunction, myalgia, N/V

Front 15

2 extra AE of nilutamide

Back 15

night (NI-lutamide) blindness and pulmonary toxicity

Front 16

Gonadotropin-releasing hormone analogs (2)

Back 16

gosrelin
leuprolide

Front 17

gonadotropin releasing hormone analog MoA and usage

Back 17

Used for hormone-sensitive prostate cancer and breast cancer
stop production of sex hormones (testosterone & estrogen).

Front 18

5 AE of gosrelin/leuprolide (GnRH analogs)

Back 18

Hot flashes, diarrhea, decreased libido, gynecomastia (male), amenorrhea (female)

Front 19

corticosteroid MoA for cancer

used where?

Back 19

Cause lymphocyte lysis
Used as part of multi-drug regimens for lymphoma and leukemia (e.g. for CHOP in NHL)

Front 20

4 corticosteroids used for cancer

Back 20

Dexamethasone Methylprednisolone
Prednisone Hydrocortisone

Front 21

Immunobiologic agents used for cancer

normally used for what

Back 21

Bacillus Calmette-Guerin (BCG) Vaccine

typically used for “tuberculosis”

Front 22

what is BCG vaccine made of

Back 22

Freeze dried preparation of attenuated Mycobacterium bovis

Front 23

how does BCG vaccine work for cancer and what cancer is it used for

Back 23

Administered directly into the bladder, which causes a local, chronic inflammatory response that leads to destruction of superficial tumor cells of the urothelium

Primary and relapsed bladder carcinoma in situ

Front 24

AE of BCG vaccine

Back 24

Risk of systemic infection, including septic shock and death

Front 25

Differentiation Agent

Back 25

All-trans-retinoic acid (tretinoin) (oral)

Front 26

MoA of differentiation agent

Back 26

Binds with the retinoic acid-1 receptor in promyelocytes in acute promyelocytic leukemia, resulting in differentiation of the leukemic blast into a more mature form which undergoes cell death

Front 27

indication of differentiation therapy with tretinoin (2)

Back 27

Acute promyelocytic leukemia- not curative, used to induce complete remission prior to BMT

Front 28

AE of tretinoin (2)

Back 28

respiratory failure
DDI with P450

Front 29

IL-2 MoA

Back 29

T-cell growth factor which promotes immunologic responses to cancer. Non-specific immune response can lead to capillary leak syndrome

Front 30

IL-2 indication

Back 30

Renal cell carcinoma

Front 31

IL-2 main toxicities (listen again) (2)

Back 31

circulatory collapse
hypotension


also CV tox, renal failure, BMS, CNS tox...

Front 32

Interferon alfa-2a and 2b MoA

Back 32

Enhances host immune response and direct antiproliferative effects on cancer cells

Front 33

interferon indications (4)

Back 33

Hairy cell leukemia, CML, melanoma, AIDS-related KS

Front 34

toxicity of interferons (2)

Back 34

Flu-like symptoms, BMS

Front 35

Rituximab - what is it and how does it work

Back 35

Recombinant humanized murine monoclonal antibody to B-cell surface marker CD20. Antibody recruits cytotoxic reaction to lymphoma cells mediated by complement activation (kills...b cells...)

Front 36

rituximab indication

Back 36

NHL of B-cell origin that express CD20

Front 37

AE of rituximab (3)

Back 37

Hypotension** (esp. 1st infusion), fever, and chills

Front 38

what is HER2 receptor and what does it do

Back 38

The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules called EGFs) to inside the cell, and turn genes on and off. The HER proteins stimulate cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably.

Front 39

trastuzamab (herceptin) MoA (targets what receptor/type of Ab)

Back 39

Monoclonal antibody to her-2-neu, a protein overexpressed on the surface of about 1/3 of breast carcinomas. Results in complement activation and subsequent cytotoxicity

Front 40

trastuzamab indication

Back 40

Her-2-neu (+) breast cancer

Front 41

trastuzamab synergy with what other drug?

Back 41

cytotoxic synergy (idk if this is good or bad but it looks like they give this drug in combo sometimes) with taxanes

Front 42

AE of trastuzamab (2)

one of these toxicities is related to another drug- indicate how you prevent it

Back 42

infusion related rxns
CV tox** in pt with prior anthracycline exposure so DO NOT GIVE WITH ANTHRACYCLINES (or if pt has been on them i think?)

Front 43

Human epidermal growth factor receptor family of chemo drugs(3)

Back 43

trastuzamab (herceptin)
cetuximab
erlotinib

Front 44

MoA of cetuximab- what receptor

Back 44

MoAB that binds specifically to the extracellular domain of EGFR. Cetuximab binds to EGFR on both normal and tumor cells and competitively inhibits the binding of epidermal growth factor and other ligands, such as transforming growth factor.

Front 45

cetuximab causes what to happen to cells? (3)

Back 45

inhibition of cell growth, induction of apoptosis, and inhibition of VEGF production

Front 46

indications for cetuximab (2)

Back 46

monotherapy or in combination with other anticancer agents in the treatment of metastatic colorectal cancer

head and neck cancer (used alone or with radiation)

Front 47

toxicities of cetuximab (2)

Back 47

infusion-related reactions** and development of an acne-like rash

Front 48

erlotinib MoA (3) indicate receptor

Back 48

Selective EGFR-tyrosine kinase inhibitor.

inhibits EGFR activity by competing with adenosine triphosphate for its binding site on the EGFR tyrosine kinase cytosolic domain, which blocks the tyrosine kinase cascade of downstream signaling

ultimately interferes with the proliferation and growth of cancer cells.

(note: difference between erlotinib and cetuximab is cytosolic vs. extracellular binding)

Front 49

erlotinib indications (indicate line of therapy) (2)

Back 49

locally advanced or metastatic non-small-cell lung cancer as a second-line agent.

Also approved for use in pancreatic cancer (idk what line)

Front 50

main 2 toxicities of erlotinib

Back 50

Diarrhea and rash

Front 51

3 DDIs with erlotinib

Back 51

Patients on concomitant warfarin (elevates INR)

increased erlotinib drug levels with inhibitors of CYP3A4

or decreased drug levels with inducers of CYP3A4, respectively.

Front 52

Bevacizumab MoA (targets what)

Back 52

Humanized MoAB directed against circulating VEGF. It binds to all biologically active circulating isoforms of VEGF and prevents the activation and promotion of angiogenesis

Front 53

usage of bevacizumab (2)

idk if have to know this

Back 53

combo with 5-FU chemo for metastatic colorectal cancer

first line treatment in combo for unresectable, advanced, recurrent, or metastatic nonsquamous NSLC

Front 54

bevacizumab AE (4)

Back 54

htn**** (less...blood vessels = elevated BP??? i doubt it)
bleeds
thrombotic events
proteinurea

Front 55

bevacizumab black box warning (3)

Back 55

GI perforation, wound dehiscence (wound breaks open along surgical suture) and fatal hemoptysis

Front 56

supportive agents used in chemotherapy are used to do what? (3)

Back 56

increase rbc
increase platelets
wbc growth factors

Front 57

2 agents that increase rbc

Back 57

EPO
darbepoetin

Front 58

agent that increases platelets

Back 58

oprelvelkin- role in cancer not defined...

Front 59

3 wbc growth factors

Back 59

sargramostim
filgrastim
pegilgrastim

GRASTIM

Front 60

3 potential roles of pharmacists in oncology

Back 60

Clinical Care
Patient education
Research

Front 61

3 areas of oncology research do i have to know this...

Back 61

Clinical
Economic
Drug discovery

Front 62

St Jude ALL studies- what did they show

Back 62

Overall survival of ALL has dramatically increased over the years

Front 63

DHFR- what's it do

Back 63

Intracellular enzyme that converts folic acid to reduced folates

Front 64

methotrexate inhibits DHFR- ultimately what does this do to cells? (what's it inhibit) (2)

Back 64

Inhibits purine and pyrimidine synthesis
Inhibits DNA, RNA and protein synthesis

Front 65

antidote to mtx

Back 65

leucovorin

Front 66

MTX xport into cells

Back 66

Active and passive transport into cells

Front 67

metabolism/excretion of mtx

which route is most important

Back 67

Primarily excreted unchanged in urine
Renal function most important

Front 68

3 metabolic pathways of mtx

Back 68

DAMPA - intestinal bacteria
7-OH-MTX (primary metabolite - inactive)
Polyglutamates

Front 69

dosing range of mtx

Back 69

7.5 mg/m2 - 35 GRAMS/m2

Front 70

dosing and schedule for MTX- low dose vs. leukemia dose vs. osteosarcoma dose

Back 70

Low dose (30 mg/m2) orally every 6 hours x 12 doses

2 gm/m2 iv over 2 hours (common for leukemia)

12 gm/m2 iv over 4 hours (common for osteosarcoma)

Front 71

renal elimination routes of mtx (2) like...what fxn of the kidney are most important for mtx elimination

Back 71

Glomerular filtration
Tubular secretion and re-absorption

Front 72

variability of mtx CL

Back 72

Clearance highly variable > 10 fold range in clearance

Front 73

Factors altering MTX clearance (2)

Back 73

hydration status
urine pH

Front 74

hydration of pt on MTX- what do you want to make sure of/monitor for fluid status (2)

Back 74

1) ensure adequate hydration- sp gravity of...urine?

2) make sure no nausea/vomiting (loss of fluids)

Front 75

urine pH monitoring (what pH do you want)

how to adjust if out of range

Back 75

urine pH must be >= 6.5

adjust with sodium bicarb if too acidic

Front 76

rationale for HD methotrexate (didn't i already make this card) (6)

Back 76

Overcome defective transport
Overcome increased levels of DHFR or altered binding affinity
Prolong drug exposure
Prevent or delay emergence of resistance
Penetrate sanctuary sites or poorly perfused tumors
can help with selective rescue of normal cells by leucovorin??

Front 77

AE of MTX (8) i'm pretty sure i have this slide

Back 77

BMS**
Mucositis
Nephrotoxicity**
Hepatotoxicity
Dermatitis
Neurotoxicity- Acute, subacute, chronic
Interstitial pneumonitis
Teratogenic

Front 78

MTX: phase that it affets

Back 78

S phase

Front 79

2 dosing factors that are very important for S phase antimetabolites

Back 79

Both concentration and TIME are important

Front 80

conc/time combinations that are equivalent

Back 80

High conc/short time = low conc/long time

Front 81

renal toxicity mechanism of MTX

Back 81

Renal toxicity - precipitation of mtx/7-OH in tubules

Front 82

4...more specific toxicities of MTX (2 are GI)

Back 82

renal tox
mucositis
GI desquamation
pancytopenia

Front 83

mucositis from MTX- severity

danger of mucositis- increases risk of...

Back 83

can be severe - increases infectious risk

Front 84

dangers of GI desquamation (2)

Back 84

infectious risk, electrolyte loss

Front 85

2 instances where you can get inadequate leucovorin rescue

Back 85

Leucovorin rescue discontinued while mtx conc still toxic

Leucovorin dose/concentration not adequate to rescue cells

Front 86

for leucovorin to be effective you must do what 3 things (I remember he was obsessed with this in pharmacology)

Back 86

Start early enough (36 to 42 hours after dose)
Provide adequate leucovorin
Continue long enough

Front 87

risk factors (for what??? MTX tox?) (3)

Back 87

Elevated MTX concentrations
Delayed MTX elimination
Drug interactions

Front 88

2 DDIs for MTX that increase risk fo tox and mechanism

Back 88

Salicylates and sulfonamides alter tubular secretion, reducing MTX elimination

Front 89

Typical MTX concentrations for low risk of toxicity (you want to keep in these rangs)

3 time points and their respective desired conc.

Back 89

24 hours after MTX dose < 10 uM
48 hours after MTX dose < 1 uM
72 hours after MTX dose<0.1 uM

Front 90

at what risk level for toxicity would you admin leucovorin

Back 90

Low risk would typically receive leucovorin


high risk too- just elevated amounts

Front 91

low risk dosing of leucovorin and when to give

Back 91

10 mg/m2 po q 6 hours x 6 doses starting at hour 36 after first MTX dose

(must start before 42-48 hours or may not see effects)

Front 92

Delayed MTX Elimination risks (4)

Back 92

Concentrations greater than prev slide
Half life greater than 3.5 hours
Inability to take adequate fluids (so MUST monitor urine output, oral intake and urine pH WHY??)

Ascites/pleural effusions (Provide site for MTX to leach out from over long period of time )

Front 93

monitor MTX conc. until it reaches what lvl (if pt has delayed MTX elimination?? i'm confuseD)

Back 93

Monitor MTX concentrations until <0.1uM

Front 94

CNS (mets?) dosing of MTX

less than 1 yr
1-2 yrs
2-3 yrs
> 3 yrs

Back 94

Less than 1 yr 6 mg
1-2 years 8 mg
2-3 years 10 mg
> 3 yrs 12 mg

Front 95

goal of dosing MTX algorithm for CNS (mets...?) - what peak MTX conc are we going for

Back 95

These doses should produce peak MTX concentrations of 10 uM.

Front 96

Pharmacist role for MTX dosing- looking to make sure pt ...(4)

Back 96

has no pleural effusions/third space
Hydrated (urine output/spec grav)
Alkalinization of urine
Drug interactions?

Front 97

monitoring for MTX (3 things)

Back 97

Monitor urine output
Monitor urine pH
Monitor MTX concentrations

Front 98

monitoring for MTX- what half life are we looking for

what conc?

Back 98

Half-life < 3.5 hours
Concentrations at 24 and 48 hours meet low risk criteria - standard leucovorin rescue- confused about leucovorin- do you always administer if there is any risk?

Front 99

MTX pt- how to treat as outpt

Back 99

Treated as outpatient with instructions to come back to clinic if emesis/lack of fluid intake

Front 100

MTX high risk of needing rescue (2 properties that indicate high risk)

Back 100

Half life > 3.5 hours
24, 48 hour MTX conc elevated