Cancer Flashcards
Most common forms of cancer?
LUng
colorectal
pancreas
breast
prostate
What is incidence?
of new cases
What is prevalence?
total # of cases
True or false, cancer rates of declined?
TRUE- rates declined BUT actual number is increasing
Characteristics of cancer cells?
uncontrollable growth
invade tissues
no differentiation
matastasize
Main difference between benign and malignant?
Benign= encapsulated, slow, some differentiation
Malignant= invasive, not differentiated, aggressive
Difference between tumour grading and staging?
Grading= how aggressive= how much differentiation
Staging= extent= has it spread
What does T,N,M mean?
T= size of primary
N= in lymph nodes?
M= metastases
What is 2 predictive biomarkers?
HER 2, BRCA
What is surgery used for?
solid tum ours
What is radiation for?
high turnover cells
What is growth fraction?
cells in cycle/Total # of cells
Why does growth fraction decrease as tumour grows?
too far from blood and nutrients
How do cytotoxic drugs work?
interfere with DNA= breaks and dies
What gene controls apoptosis?
p53
I have a phase specific agent what is important for dosing?
multiple repeated doses
What type of tumours is cell cycle specific drugs for?
high growth factor
What is important for cell cycle non specific drugs?
dose dependent
What are some trial endpoints for cancer?
overall survival=1
QoL
safety
If therapy is induction what does that mean?
primary treatment
What happens first usually for adjuvant therapy?
surgery or radiation first
What is the premise of adjuvant therapy?
a lot less cancer cells= more susceptible to chemo
What is consolidation therapy?
same as adjuvant but for liquid cancer
What does Neo-adjuvant mean?
prior to local treatment
What is salvage therapy?
for relapse
What is SCT for?
overcome resistant tumour
WHat is lymphodepleting used in?
CAR-T to create spass for CAR T cells
Common s/e of cancer meds?
neutropenia, alopecia, NV, fatigue
How do you dose cancer drugs, and MABs?
Cancer drug= BSA
MABS= mg/kg
In order to combat neutropenia from bone marrow damage what can we give?
filigrastim= WBC growth factor
Why does chemo fail?
cannot get 100% of it killed, kills be %, toxicity, comorbs
Ways of resistant mechanisms?
enzymes to inactivate
pump drug out
repair damage
mutation in receptor
use different pathway
What drug blocks ER?
tamoxifen, fulvestrant
What drug blocks aromatase?
‘trozoles’
What drug inhibit estrogen production?
relin, megestrol
What blocks TESTosterone receptor?
bicalutamide
Stops Test production?
relins
WHat do imatiNIB do?
small molecule that acts within cancer cell
What do MABs do?
block extracellular proteins or receptors
How can we affect receptors with mass?
block, block antibodies, bring toxins,
What is the most important thing with targeted therapy?
BIOPSY
What are the PD-1 inhibitors? What does it do?
pemrbolizumab, nivolumab
blocks self recognition and allows T cell to kill
What was the first targeting cancer med?
tamoxifen
How does tamoxifen work?
blocks ER= estrogen doesn’t stimulate proliferation
IN regards to different tissues what is special with tamoxifen?
antagonist in breast BUT agonist in uterus= uterine cancer risk
What women get tamoxifen?
PREmenopausal (due to heart risks) and ER/PR positive
What is dose of tamoxifen?
20mg daily= max efficacy
How long is tamoxifen therapy for usually?
5 years but if high risk 10
If breast cancer and post menopausal what agent do we use?
aromatase inhibitors
s/e of tamoxifen?
hot flashes, N, mood, arthralgia, vag dryness, DVT, uterine cancer
What s/e of tamoxifen does the body get used to?
nausea
Can patients use NHP estrogens for side effects?
FUCK NO
What interactions are an issue for tamoxifen?
activated by 2D6=0.321 wk bupropion, fluoxetine, paroxetine
How does letrozole work?
stops conversion of androgens to estrogen
What other women may use letrozole over tamoxifen?
if suppressed or no ovaries
What AI is irreversible?
exemastane
What AI has the worst CYP interaction?
3A4 with exemastane
Stand out s/e of AI?
MORE tolerable menopause like s/e
LESS DVT risk
OSTEOPOROSIS
How does Goserelin work?
GnRH AGONIST= suppress ovarian function
What must goserelin be combined with?
AI
Prostate cancer sx?
issues urinating, urge, pain, blood, no erection
GENERAL prostate cancer options?
GnRH AGONIST
GnRH ANTAGONIST
CYp17 inhibitor
Antiandrogens
get T to castration levels
Issue with GnRH agonists?
initial flare period before down regulation of axis
What is prescribed for initial flare?
bicalutamide!!!
If mild cancer what is duration of GnRH?
max 3 years
What are the GnRH agonists?
goserelin and leuprolide
What is the prostate GnRH antagonist option?
degarelix= rapid decrease
In regards to dosing of GnRH agonists and antagonists what is different?
agonists= inj 3-6 months
antagonists= inj monthly
s/e of androgen deprivation?
uriniary issues, man boobs, hot flashes, libido issues, weight gain, tired, OP, MI
How does Abiraterone work?
inhibits CYP 17= less T production
What is abiraterone used with? WHY?
PREDNISONE= prevent rise in ACTH(HTN, low K)
What is considered resistant prostate cancer?
3 consecutive increases of PSA or bone lesions despite ADT
What are the androgen blockers?
‘Lutamides’
What 2 androgen blockers also inhibit AR binding to DNA?
enzalutamide and apalutamide
What does this mab mean, bivicizumab?
Ci= circulatory
zu= humanized
What does this mab mean, amliximab?
li(m)= immune system
xi= chimeric
What does this mab mean,tertumumab?
tu= tumour
mu= fully human
What type of MABs have less infusion reactions?
fully humanized ones
How much is a mab human if humanized vs chimeric?
humanized= >90
chimeric=>65
When do we use pertuzumab and trastuzumab?
HER 2+
When do infusion reactions happen?
generally within 30m-2 hr BUT monitor for 24 hours
Infusion reaction sx?
fever, itchy, chest discomfort, NVD, rash, pain, AND CYTOKINE RELEASE SYNDROME(BAD)
Can you cure follicular lymphoma?
NO
What do we use in Follicular lymphoma? What has evidence to be added for greater efficacy?
anti-CD20 PLUS rituximab or obinutuzumab
When do we prefer obinutuzumab over rituximab?
if intolerant/resistant to rituximab
MOA of rituximab?
cytotoxic through phagocytosis, directly, antibody
What is rituximab resistance?
progression within 6 months of last dose
How does Blinatumomab work?
CD19 of b cells and CD3 of T cells to recruit immune system
What are the EGFR inhibitors? How do they work?
cetuximab and panitumab
- prevent dimerization
What is cetuximab combined with?
irinotecan
What cancer often uses EGFR inhibitors?
colorectal
What RAS is cetuximab indicated in?
wild type
Benefit of panitumumab over cetuximab?
more humanized= no need for premedication
How does bevacizumab work?
VEGF inhibitor
s/e of bevacizumab?
HTN, bleeding, MI
what was the first VEDF inhibitor?
bevacizumab
IMportant PK of bevacizumab?
LONG half life
What side of the colon does most cancers happen?
LEFT
Which type of colon cancer is bevacizumab better in?
right sided
What drug works of VEGF2?
ramucirumab
What is considered HER 2+
3+ staining
MOA of trastuzumab?
block dimerization
MOA of pertuzumab?
block heterodimerization
S/e of HER2 therapy?
HF
What is T-DM1?
trastuzumab with cytotoxic agent called emtansine
MOA of enfortumab?
Nectin 4= urothelial cancer
What is a benefit of immunotherapy over other chemo?
better cancer response for longer, because more response with each cycle
What is the CTLA4 inhibitor?
ipilimumab
What are the PD-1 inhibitors?
Pembrolizumab
Nivolumab
What are the PDL-1 inhibitors?
Durvalumab
atezolizumab
avelumab
Where do CTLA4 and PD inhibitors act?
CTLA4= lymph
PD-T= cancer cells
How does CTLA4 work?
if it binds the T cell is innactivated and cancer can proliferate
When is CTLA4 inhibitors used?
Melanoma, kidney, lung
Where is PD-1?
Tcells
Should you use both PD1- and PDL-1 inhibitors?
Overkill not needed
If toxicity with IO what can we do?
ONLY HOLD DOSE or stop[
Survival of melanoma?
bad but with IO much better
What is the majority of lung cancer?
NSCLC
What tests and what value indicates PD-L1 susceptible?
TPS >50%
IN regards to s/e and when they go away what is important with IO therapy?
can self perpetuate and continue after d/c
s/e of IO?
rash, colitis, hepatitis, eye, myocarditis, gi, renal
How often should lab monitoring be?
q3months and even after termination
When are side effects seen in IO and why?
weeks to months because it takes time for immune system to kick in
I have grade 2 s/e from IO what do we do?
halt drug for a bit
I have grade 3 s/e from IO what do we do?
CS and halt drug
I have grade 4 s/e from IO what do we do?
d/c drug
If s/e from IO is not responding to CS what do we use?
infliximab
What is dose of CS for grade 2 s/e of IO?
0.5 mg/kg/day of prednisone
What is dose of CS for grade 3/4 s/e of IO?
1-2 mg/kg/day of prednisone
Which s/e get quick relief from CS in IO?
gi, hepatic and renal toxicity
Why does classic chemotherapy have bad side effects?
targets all rapidly dividing cells= like gut, mucosa, hair
Urgent s/e of cancer therapy?
bleeding, severe vomit and diarrhea, dyspnea, chest pain
Long term s/e of cancer therapy?
infertility, HF, OP, cataracts, fatigue
If grade 3 toxicity what do we know?
bad and interferes with eating/ life
What is a grade 4 toxicity?
needing hospital, life threatnening
Drugs that have the most hypersensitivity issues?
taxans, platinums, MABS
How do we treat hypersensitivity?
pretreat with steroid, famotidine, antihistamine and acet
What is the most dose limiting toxicity?
myelosuppression
What does myelosuppression lead Tod?
anemia-low RBC
Neutropenia= no WBC
Thrombocytopenia= bleeding
What is a nadir period?
lowest point of blood cells
How to we treat anemia? What DONT we give?
infusion of RBC
NO EPA
Why is anemia so prolonged in cancer therapy?
cumulates as RBC live for 120 days so takes a while to notice
How do we treat thrombocytopenia?
transfusion
What is too low ANC?
under 1.5
How do we treat neutropenia?
filigrastim or pegfiligrastim
A patient just finished their first cycle what myelosuppression are they at risk of?
febrile neutropenia
Why don’t we want to treat fever in cancer patients?
only way to tell if they have an infection
How low is too low for just neutrophils?
<0.5
If patient has febrile neutropenia what should they do?
ER!!! need antibiotics
What antibiotics are used in febrile neutropenia?
antipseudomonas= pip/taz, meropenem, ceftazidime
Gram Pos= vancomycin
When may we want to cover gram positive in febrile neutropenia?
MRSA carrier, skin infections, sepsis
How can a cancer patient prevent infections?
hygiene, protect skin, reduce exposure, mouth care
Difference between filigrastim and pegfiligrastim?
Peg= long acting
At what risk should you do primary prevention of febrile neutropenia?
> 20%
When does mucositis usually start?
a week into therapy
What does mucositis lead to?
depression, infection, nutritional issues, pain
How can we help with mucositis?
hygiene tups, salt rinses
Ice chips= sometimes CI
anesthetics
What mouth washes are a no go?
alcohol
ANDMAGIC MOUTWASH= bas thrush
How to help with dyspepsia?
usual therapies
What agents have the most diarrhea?
irinotecan, FU
Non pharmacist for diarrhea?
small frequent meals, avoid insoluble fibre, increase soluble fibre, avoid pop/juice
Drugs for diarrhea?
loperamide
octreotide- lowers fluid secretion
How to treat acute diarrhea?
atropine due to cholinergic causes
How much loperamide before see doc?
if no resolution in 24 hours
What for constipation?
senna, PEGH
Warning signs for contestation?
no BM in 3-5 days, no farts, blood, foul vomit
What do patients say they taste after chemo?
metallic or chemical taste
What drug causes HFSR the most? And how does this relate to therapy?
capecitabine
usually if get= more response
How to treat HFSR?
NOTHING
prevent thru lower heat, moisturizer, gloves
What drugs cause the most alopecia? What’s different?
doxorubicin- reversible
paclitaxel- sudden total
docetaxel- irreversible
What happens to eyelashes if alopecia?
comes back wired and rough
How to treat peripheral neuropathy?
AD, opioids, anticonvulsants- gabapentin
What drugs cause peripheral neuropathy?
taxans, IO, PIs
What drugs commonly cause heart issues?
FU, trastuzumab
Is it easier to prevent or treat nausea?
DUH prevent
Which type of nausea/vomiting is serotonin dependent? What agent would we use?
Acute= 24hours, 5HT antagonist
Which type of nausea/vomiting is Substance P dependent? What agent would we use?
delayed=>24 hours
use NK1 antagonists
What agent would we use for anticipatory nausea? When do we give it?
Lorazepam the NIGHT before
Worst causer for delayed nausea?
cisplatin **KNOW
Patient characteristics that put you at risk of chemo induced nausea?
Low alcohol tolerance, younger, female, history of motion sickness or nausea during pregnancy
What are the 5HT antagonists?
Ondansetron ‘setrons’
What is the 4 drug backbone for nausea treatment for high risk?
5-HT3
NK1
CS
Olanzapine
S/e of ondansetron?
COnsitpation, headache, QT
What is the second generation 5 HT3? What’s. the benefit?
Palonosetron
Longer acting, LESS QT
What drug is used for NK1? what’s special?
Akynzeo- netupitant with palonosetron
Important interaction with akynzeo?
dexamethasone needs a 50% dose reduction
Dosing of akynzeo for high risk emetic patient?
1 dose prior to start of cycle of chemo with dex then dex for 3 extra days
Dosing of akynzeo if on carboplatin (>4 AUC) or anthracycline/cyclophosphamide?
1 dose prior with dex no more dex after
S/e of akynzeo?
well tolerated but constipation, tired, headache
What CS is used for nausea?
Dexamethasone
Dose of dexamethasone both with and without akynzeo? and for acute vs delayed?
Normally 20 mg but with akynzeo =12 mg
delayed= 8 mg
Why do we use olanzapine?
effective for delayed but also used for breakthrough
S/e of olanzapine?
raise BG, sedation, weight gain
Which is better, olanzapine or metaclopramide for chemo induced nausea?
Olanzapine
How does metaclopramide work?
dopamine antagonist
S/e of metaclopramide?
sedation, restless, diarrhea
If using lorazepam for nausea what type is it for?
Anticipatory
What is abosuletly last line for nausea?
Nabilone- cannabis
What AUC of carboplatin is considered high emetic risk?
> 4
What is the percentage of people that get get nausea in high-low emetic risk?
HIgh=>90
Medium=30-90
Low= 10-30
What IV chemo drugs are high emetic risk? What are the example?
cisplatin and A/C
doxorubicin and cyclophosphamide
Dose of olanzapine for pre treatment?
5 mg
If medium risk for acute what is emetic treatment?
All but no olanzapine
If high risk both AC treatment and not, what is therapy for delayed nausea?
NOn AC= Olanzapine and dex
AC= olanzapine
If medium to low emetic risk do we give stuff for delayed nausea?
NO
If moderate and not carboplatin what drugs for acute nausea?
Dex and ondansetron
If low risk what drugs for acute?
ondansetron OR dex OR meaclopramide
What is recommended for breakthrough nausea? What conditions apply?
Olanzapine 10 mg IF not previously used for prophylaxis
If olanzapine has already been used and we need breakthrough nausea management what can we do?
metolopramide is fine but increase dex better
try gransitron over other
increase olanzapine
Best way to prevent anticipatory nausea?
control of acute and delayed
