Therapeutics Exam 2 Pt. 2 (Weddle) Flashcards
Prostate Cancer: Main etiologies? Hormonal:\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_ receptor alterations Enzyme \_\_\_\_\_\_\_ is key to synthesis of the hormone can be genetic (small % tho)
testosterone hormone….
Androgen receptor alterations (amplification/overexpression; mutations; splice variants)
enzyme: CYP17A1
Prostate Cancer: Risk Factors:
Age: increases with increasing age
Race: more common in ______ (thought to be due to differences in androgen receptors and testosterone production)
Family Hx: increased risk with first degree relative
Others: ?
race: African Americans
Others:
Diet - high fat = higher risk
Occupation - textile and other industrial workers = increased risk
(long term vasectomy– but like no because maybe they are been screened more/have an urologist)
Prostate Cancer:
what things may have a Protective effect?
Vit. E
selenium
soy
lycopenes
screening options for Prostate Cancer?
DRE (direct rectal exam) (nose feeling = normal; chin = more of concern)
PSA (prostate specific antigen)
(TRUS - transrectal ultrasonography = bad specificity and sensitivity)
PSA levels:
normal: ______
needs evaluation: ______
Highly suspicious of malignancy: _______
OR is PSA velocity (change in a year) is _______
normal: 0 - 4 ng/mL
eval: > 4
suspic for malignancy: > 10
PSA velocity: > 0.75
Factors of PSA levels:
what will decrease PSA
finasteride and dutasteride
Factors of PSA levels:
what will increase it
ejaculation/prostatic manipulation or biopsy
BPH
prostatitis
ACS Screening Guidelines for Prostate Cancer:
Men > _____ y.o should get a PSA +/- DRE
50 years old!
ACS Screening Guidelines for Prostate Cancer:
once a man gets a PSA:
if his PSA is < _____ they should get the PSA checked every 2 years
or
if his PSA is > _____ they should get the PSA checked every annually
if < 2.5 - Q 2 years
if > 2.5 - then yearly
Discussion of screening of prostate cancer should happen earlier in high risk patients —
who is high risk and when to start screening
if african american - higher chance - start at age 45
if several first degree relatives - maybe start at 40 y.o
T or F: Finasteride but not dutasteride is approved for prostate cancer prevention
FALSE! neither of them are
there were trials for them but like not FDA approved
Finasteride trial finding in relation to prostate cancer prevention?
did reduce risk BUT people who did get prostate cancer had disease with a higher GLEASON score (aka more aggressive and less differentiated)
but maybe because prostate had shrunk – they could get better biopsies and diseases looked worse..?
what is the current recommendation for prostate cancer prevention?
there is not one :’(
Prostate Cancer Pathophys:
the _______ passes through the prostate and prostatic hypertrophy may compress it
urethra
Prostate Cancer Pathophys:
compressing on the urethra may lead to what things related to urination?
increaesd frequency inability to start and stop flow dysuria hematuria nocturia incomplete bladder emptying dribbling
Signs and Symptoms of Prostate Cancer:
asymptomatic early on... but advanced disease: alterations in urinary habits impotence lower extremity edema weight loss anemia
Prostate Cancer:
Metastasis to the ______ is most common but can also go to liver and lung
bone
99% of Prostate Cancer is ______
what kind of histology
adenocarcinoma
Explain Gleason Score
can be 2 - 10
get 2 diff scores (1 -5) from the primary and secondary growth patterns then add them together
higher score = higher risk of exracapsular spread
Gleason Score:
scores of _____ = slow growing and well differentiated
scores of ____ = aggressive and poorly differentiated
2 - 4 = slow
8 - 10 = aggressive
TNM staging for prostate:
T is referring to the _____ of the tumor
the spread of it/how extended it is (like if on both lobes or not)
T is not referring to size per se
what are the overall possible treatment options for prostate cancer
observation
active surveillance
Radiation therapy - external beam = ERBT
brachytherapy - implantable radiation therapy
Radical Prostatectomy + PLND (pelvic lymph node dissection)
ADT (androgen deprivation therapy)
How to do observation treatment for prostate cancer pts
PSA and DRE Q 6 mos
just monitor the course of disease - expect to deliver palliative therapy for development of sxs or change in the monitoring
(usually someones heart will kill them before prostate cancer will…. so like we dont have to freak if we suspect something)
Pros and Cons of observation therapy of prostate cancer pts
pros: avoids immediate morbidity assoc. w/ treatment
cons: risk of disease complications such as urinary retention or fractures
complications of radiation therapy of the prostate cancer pts?
bladder/rectal sxs
erectile dysfunction
radiation proctitis
idea behind active surveillance of prostate cancer pts
monitor PSA, DRE, Sxs
tx is initiated with any rising PSA or development of sxs….
radical prostatectomy and PLND:
is ________ therapy
use this method in men who _______
definitive curative therapy
men who have life expectancy > 10 years
Androgen Deprivation therapy for Prostate Cancer:
Goal is to induce ______ levels of testosterone
castrate levels
aka < 50 ng/dL after 1 month of therapy
ways to induce andgrogen deprivation therapy in prostate cancer
surgically: orchiectomy (remove da testis)
medically: LHRH agonists
antiandrogens (-tamides) - block androgen receptor
LHRH Agonists Toxicities of Prostate Cancer:
Acute Toxicities?
tumor flare, gynecomastia, hot flashes, erectile dysfunction, edema, injection site reaction
LHRH Agonists Toxicities of Prostate Cancer:
Long term Toxicities?
Osteoporosis/fracture!! obesity
insulin resistance
changes in lipids
increased risk in diabetes and CV events
since LHRH agonists can cause a flare at the beginning of the therapy and this can be really bad (esp in metastatic disease) - what can we do to help
give antiandrogens first!! for like 7 days..
Symptoms of tumor flare in prostate cancer due to LHRH agonists
Bone pain (bc metastasis) Increased urinary symptoms
what is the most common anti-androgen therapy (anti androgen receptor) and why
biclutamide
b/c QD and less ADEs
what drug is a LHRH antagonist
degarelix
why is degarelix better than LHRH agonists (leuprolide or goserelin)
drops testosterone very fast - 7 days – and NO tumor FLARE!!!
CAB in metastatic prostate cancer?
CAB = combined androgen blockade
using two diff androgen related therapies (anti-androgen and LHRH agonists) — this will lead to more toxicities
what is the standard of care for chemo combo treatment options for metastatic prostate cancer
docetaxel and ADT
use the docetaxel and ADT combo in metastatic prostate cancer when??
when pt has high volume disease!!
aka visceral or 4+ bone metastases
idea behind intermittent androgen deprivation
monitor PSA and when they return to a pre-specified baseline (ex: < 4) then stop the androgen suppression and keep monitoring PSA and when at another high level (ex: >10) - start the meds again
good because decreasing exposure/ giving pts a break - decreased cost and decreased side effects
intermittent seen to be as effective…
what is metastatic CRPC?
CRPC = castrate recurrent prostate cancer
even though hormone free pt is still progressing
all pts become hormone refractory
what is Sipuleucel? and what is it used for
Sipuleucel used for metastatic CRPC (asymptomatic or minimally symptomatic)
it is where you take out APCs then give the PAP-GM-CSF
1st line for metastatic disease regimen for prostate cancer
what is 2nd line?
docetaxel and prednisone
2nd: cabazitaxel (it is PGP resistant!!)
Abiraterone MOA?
irreversibly inhibits CYP17
an enzyme involved in androgen synthesis
Abiraterone: must be given with ______ and why
prednisone
to prevent adrenal insufficiency
Abiraterone: take with or without food?
without food!
Abiraterone: CYP interaction
CYP3A4
Enzalutamide: MOA?
androgen binding is blocked
Enzalutamide:
caution in pts with ______ history
seizure
when is Enzalutamide used?
when pts have failed doxetaxel
used in metastatic CRPC
Enzalutamide: give with prednisone?
NO!! (give prednisone with abiraterone)
Toxicities of Enzalutamide?
fatigue/falls/weakness!
diarrhea/hot flashes/ muscoskeleteal pain, HA, HTN
Metastatic prostate cancer — what is 1st line for pts that are castration NAIVE
abiraterone + prednisone
Radium 223 Dichloride:
forms complexes with _____ areas with increased _____ turnover
bone; bone
Radium 223 Dichloride:
use by itself or with chemo too?
by itself!! b/c ADE’s would be too wild
ADEs - anemia,neutropenia, thrombocytopenia
Radium 223 Dichloride:
approved for what related to prostate cancer?
related to symptomatic bone metastases for CRPC
but no known visceral metastatic disease
Current recommended screening for lung cancer:
low dose CT scan for pts age 55- 75 who have 30 pk hx of smoking and still smoking or quit w/in past 15 years
there was a trial that showed that ______, a supplement/herbal increased lung cancer risk
beta carotene
4 main mutations seen in EGFR? which one is seen in smokers?
EGFR, ALK, ROS-1
K-RAS (seen in smokers)
also check for BRAF and PDL-1….?
PD-L1 Status:
Testing is not recommended for NSCLC or SCLC?
not recommended for SCLC
NSCLC vs SCLC:
has a clear relationship to smoking?
SCLC
NSCLC vs SCLC:
has slower growth fraction
NSCLC
NSCLC vs SCLC:
rapid cell growth fraction
SCLC
NSCLC vs SCLC:
highly sensitive to chemo/radiation
SCLC
NSCLC vs SCLC:
moderately sensitive to radiation/chemo
NSCLC
NSCLC vs SCLC:
commonly see paraneoplastic syndromes
SCLC
what are some paraneoplactic syndromes?
*typically seen in SCLC
overall they are nonmetastatic systemic effects that accompany malignant disease
ex: cushing’s syndrome, hypercalcemia, SIADH
T or F: In lung cancer: pts who have EGFR mutations, ALK or ROS-1 rearrangements typically do not have PD-1 expression
True!!!
____ testing is not recommended for SCLC
_____ is recommended to test in first line metastatic setting for NSCLC
(what types of mutations)
do not test for PDL1 in SCLC
BRAF V600E: recommended fro NSCLC
Histology/pathology Subcategories of NSCLC and SCLC
NSCLC: adenocarcinoma, squamous, large cell
SCLC: small cell…
NSCLC Histology Subcategories: (adenocarcinoma, squamous, large cell)
which one of them is related to smoking, which one is related to non smokers and which one is usually located peripherally to the lung
smoking: squamous
adenocarcinoma: non smokers
peripheral: large cell
staging of SCLC?
limited or extensive….
extensive = metastasis
SCLC will progress (slowly or quickly) and is (resistant or sensitive) to chemo/radiation
progress quickly;
is sensitive
Treating SCLC Limited stage disease:
Combined treatment of ______ is used but maintenance chemo is not valuable
Prophylactic _____ radiation should be considered because lots of ppl form metastases here
radiation and PLATINUM based combo chemo
brain
Treating SCLC extensive stage disease:
_____ based combo chemo (with or without) radiation is preferred
platinum
without
*like limited stage but no radiation
Treating SCLC extensive stage disease:
if brain metastases are present — do what?
maintenance therapy - yay or nay?
metastases = brain radiation therapy
nay to maintenance
Commonly used chemo regimens for SCLC?
platinum dublets!!
EP, EC, Cisplatin/Irinotecan, Carboplatin/Irinotecan
what is the EP chemo regimen
cisplatin
etoposide
what is the EC chemo regimen
carboplatin
etoposide
cisplatin based regimens - biggest complications:
________ failure
renal
NSCLC:
______ is the most efficacious modalities for treating
surgery
NSCLC:
T or F: adjuvant chemo has benefits
true!
surgery and chemo is dope for NSCLC
(Surgery is SCLC - not as dope)
T or F: NSCLC does not get maintenance therapy just like SCLC
false!!
NSCLC can get maintenance but SCLC extensive does not…
if pt has NSCLC and it is a IIIB/IV cancer - what was the treatment option?
IIIB/IV is unresectable and thus do the platinum dublet
carboplatin less toxic than cisplatin!!
if treating metastatic NSCLC: consider what for therapy
if adenocarcinoma/squamous
and consider mutations!!
what agents are for EGFR
afatinib
erlotinib
gefitinib
osimeritinib
what agents are for ALK
alectinib
certinib
brigatinib
criozitinib
what drugs are for ROS-1
crizotinib
certinib
what drugs are for BRAF V600E
dabrafenib + trametinib
tram - is actually MEK but used with BRAF therapy!!
Tyrosine Kinase Inhibitors Review:
EGFR mutations are in exons ____ and ____
19 and 21
Tyrosine Kinase Inhibitors Review:
________ is used for the T790M mutation
osimertinib
A pt does not have the t790M mutation but does have an EGFR mutation – can you use osimertinib?
yes!
what ALK targeting therapy is first line?
alectinib
for the ROS-1 therapies what is 1st line and what is 2nd line
1 - Crizotinib
2 - Ceritinib
For treating metastaic lung cancer: if no mutation or chemo has been exhausted…
check _______
if it is > 50% give -______
check PD-L1
give pembrolizumab
Pembrolizumab or nivolizumab is 1st line?
pembro
immunotherapy toxicities? (from drugs of PDL1 and CTLA4..)
-itis
pneumotitis, hepatitis, nephritis (THESE ARE DELAYED REACTIONS!!)
what are the genetic factors related to melanoma
FAMMS (familia atypical multiple mole syndrome)
HDNS (hereditary dysplastic nevus syndrome)
Sunlight is obvs a risk factor for melanoma - but which UV is especially damaging
UV B
A may play a role as well tho..
Melanoma:
ADA recommends ____ self exams
monthly!
melanoma types:
superficial spreading melanoma?
appears flat but becomes irregular and asymmetrical
melanoma types:
nodular?
vertical growth only - more aggressive!!
melanoma types:
lentigo maligna?
BROWN or black lesion (like tan spot on face of the elderly)
melanoma types:
acral lentiginous?
in weird places:
on palms, soles, under nail beds
melanoma types:
uveal melanoma?
on da eye
where does uveal melanoma typically metastasis in?
the liver!
the one on the eye goes to the liver??
Melanoma:
_____ is curative therapy
______ is only used in palliative setting
surgery
radiation
Treatment overview for melanoma:
IB/IIA
or IIB/IIC
or III
Or unresectable
IB/IIA: clinical trial or observation
IIB/IIC: clinical trial, observation or INTERFERON
III: observation, immunotherapy!!!(nivolumab or HD ipilumimab /dabraf/tram) /interferons
unresectable: T-VEC!
symptom management of ipilumimab toxicities
if grade 1?
symptom control - NO STEROIDS - keep on the anti CTLA4 therapy
symptom management of ipilumimab toxicities
if grade 2?
symptom control - NO STEROIDS - wait on the anti CTLA4 therapy til back to grade 1 toxicity
if it does not get back to grade 1 - treat like grade3/4
symptom management of ipilumimab toxicities
if grade 3/4?
hold anti CTLA4 therapy!
give high dose steroids!!!! then taper of steroids for a long ass time.. may give infiximab if no response from steroids in 2 -3 days
interferon alpha used to be the only immunotherapy option for melanoma — but it sucked - why?
suuuuuper toxic and at high doses but not super effective
toxicities: Depression/suicidal ideation; hepatic/hematologic toxicity; fever/flu-like sxs; severe fatigue
what are the first line metastatic melanoma options?
nivolumab; nivolumab/ipilimumab
pembrolizumab
dabrafenib/tramietinib
vemuraf/cobimeti
aka NO CHEMO DRUGS
do immunotherapy
Melanoma treatment:
deciding on treatment:
always start with ______ for a quicker set of action
_______ can take weeks to see effect
start with targeted oral - it is faster
immunotherapy_ can take weeks
unique toxicity vemurafenib and dabrafenib?
may develop squamous cell carcinoma!!
Trametinib is good with dabrafenib - why?
will decrease time til resistance develops b/c tram. works downstream from BRAF
also it will decrease squamous cell carcinoma
IL-2:
can be used in melanoma ——–but we dont but why tho
toxic af and hella high dose
and LIFE THREATENING CAPILLARY LEAK SYNDROME
if they get it - they get it in the ICU
Histology of Testicular Cancer:
Most (95%) of testicular cancers are ______ tumors and are divided into 2 major histology types: ______ and ______
germ cell;
seminoma; non-seminoma
Histology of Testicular Cancer: Seminoma or Non-Seminoma - which one resembles primordial germ cell tumor common in4th decade of life secretes b-HCG ONLY
seminoma
Histology of Testicular Cancer: Seminoma or Non-Seminoma - has 4 histopathologic subtypes (embryonal, yolk sac, choriocarcinoma, teratome) common in 3rd decade of life may secrete b-HCG and a-FP (fetoprotein)
non-seminoma
Histology of Testicular Cancer:
Seminoma or Non-Seminoma -
which one is more aggressive
non-seminoma
Risk factors of testicular cancer?
cryptorchidism (undescended testicle)
maybe kleinfelters syndrome
signs/sxs of testicular cancer
________ mass
_______ to antibiotics
ultrasound will reveal a ______ mass
painless testis
NOT responding to abx
hypoechioc mass
Testicular cancer:
is _______ growing (slow or rapid)
rapid!! - treat ASAP!
Testicular cancer:
T or F: best method for diagnosis is needle biopsy of da scrot
false!!!
never do this! it can contaminate lynphnodes and lead to metastatic disease!!
Testicular cancer:
what are tumor markers to look at post-orchiectomy and with metastatic therapy?
AFP and beta-HCG can be increased by testicular cancer!!
what are some other factors that may increase beta-HCG
prostate, bladder, ureteral cancers and MARIJUANA absue
T or F:
Chemo penetrates the testis super well and is first line for early stages of testicular cancer
FALSE!
chemo doesnt get to the testis well
1st line is radical orchiectomy
what are the common testicular cancer regimens (just initials listed as answer)
BEP
VIP
VeIP
what does the BEP regimen consist of
this is used notably in testicular cancer
bleomycin(b)
cisplatin (p)
etoposide (e)
what does the VIP regimen consist of
this is used notably in testicular cancer
cisplatin (p)
ifosphamide (I)
etoposide (the V because of whatever its brand name is)
MESNA! bc ifosphamide
what does the VeIP regimen consist of
this is used notably in testicular cancer
cisplatin (P)
ifosphamide (I)
vinsblastine (Ve)
MESNA! bc ifosphamide
If a patient relapses their testicular cancer —-
what is the main treatment option/salvage therapy
high dose chemo + stem cell transplant!!!
what are the steps of salvage therapy/ high dose chemo for relapsing testicular cancer (some flow chart pic in the notes)
collect blood stem cells? (PBSC and give G-CSF)
then give 1 cycle of chemo (Caroplatin and etoposide days before transplant!) “Day -5, -4 -3”
then PBSC re-infusion and filgrastim “Day 0”
do more PBSC collecting if needed
then do cycle 2 of HD chemo
late effects of toxicities of testicular cancer treatments
sterility neuropathy (vinblastine!!) nephrotoxicity (platins!!) pulmonary fibrosis!! (BLEOMYCIN bish) vascular toxicities secondary malignancies
Ovarian Cancer:
possible etiology?
“incessant ovulation”
more ovulation = more disruption and epithelial fixing in the ovaries
things that will increase ovarian cancer risk?
early menarche/late menopause - aka more time for ovulation
increased age
nullparity (aka constant ovulation no break because not pregnant)
in-vitro fertilization (bc given ovulation stimulating factors)
2 + 1st degree relatives with ovarian cancer
genetic factors: BRACA and p53
HPNCC
caucasian race
what is HPNCC and how does it relate to cancers?
HPNCC = hereditary nonpolyposis colorectal cancer
this is a familial predisposition and increases endometrial cancer and ovarian cancer
things that will decrease ovarian cancer risk?
multiple pregnancies
prolonged use of oral contraceptives ( >50% risk reduction if used for over 5 years)
prophylactic ooporectomy
Ovarian cancer:
screening options?
no effective screening tool :’(
(known as the silent killer!!!)
just do prevention (like oral contraceptives 5+ years and have kids….)
or do prophylactic ooprhrorectomy if pt has BRCA mutations
Biggest con with ovarian cancer presentation/
usually asymptomatic and then when they do have symptoms they are very general/non-specific and are like similar to PMS/period symptoms…
what is the typical first line treatment for ovarian cancer?
surgery + adjuvant chemo!!
usually can cure easily but relapse is typically quite quick
Ovarian cancer surgery is called _______ surgery
debulking!
lots of things removed! the peritoneal is messed with because apparently the cancer likes to go there
Surgical outcomes of ovarian cancer:
patients are either _______ or ______
and which one is related to poorer prognosis
either: optimally debulked or sub-optimally debulked
sub-optimal = poorer prognosis duh
optimally debulked and sub-optimally debulked:
how are the two differentiated
optimal = < 1 cm of disease left
sub - optimal = > 1 cm of disease left
current standard chemo for ovarian cancer?
carboplatin and paclitaxel Q 3wk
and get like 6 cycles of chemo
also seen that carboplatin Q3 weeks and paclitazel dose dense weekly was effective too!!!
Ovarian Cancer dosing of Carboplatin:
elimination of carboplatin closely mirrors _____
and then the dosing uses the _____ equation
mirrors GFR
Calvert equation
what is the calvert equation?
used for carboplatin dosing in ovarian cancer –
carboplatin dose = AUC x (GFR +25)
*AUC is decided by the Dr (5 - 7.5)
what is IP chemo?
intraperitonieal chemo
used in ovarian cancer!!!
why use IP chemo?
increase tumor exposure but decrease systemic toxicity
bad things about IP chemo?
grade 3/4 toxicities were worse vs IV only chemo
v. toxic
dumping 2 L of fluid into da abdomen = discomfort
who will probably not handle IP chemo well?
poor performance status pts
Stage IV disease! (used in Stage III ovarian cancer tho!!)
> 65 y.o
Metastatic Disease - Ovarian Cancer:
Recurrence definitions
Platinum sensitive vs platinum resistant vs platinum progressive?
sensitive = relapses > 6 mos after completing initial platinum regimen
resistant = relapse < 6 mos after completing initial platinum regimen
progressive = no response or progressed during primary therapy…
*if sensitive – use the regimen again!!!
3 PARP agents approved in ovarian cancer?
olaparib
rucaparib
niraparib
indications for all the PARP inhibitors?
olaparib
rucaparib
niraparib
ola: BRCA mutation ovarian cancer and tried 3+!!! agents
OR maintenance of complete or partial response to pt based therapy
ruca: BRCA mutation ovarian cancer and tried 2+!!! agents
OR maintenance of complete or partial response to pt based therapy
nira: maintenance only!!
must monitor what with Niraparib?
CBC, BP and HR!!
b/c ADE’s = myleosuppression and HTN and HTN crisis
Pathophys of HCM? (hypercalcemia of malignancy)
increased PTHrP (parathyroid related protein) increased calcitriol increased resorption decreased elimination bone metastases
HCM etiologies
humoral!!! (because PTHrP) local osteolytic hypercalcemia Vit. D secreting lymphomas ectopic hyperparathyroidism renal
Signs and Symptoms of HCM:
Mild:
Moderate:
Severe:
mild: polyuria/polydipsia
Moderate: dehydration/lethargy/confusion/EKG changes
severe: seizures, coma, arrhythmias
corrected calcium eqn?
Serum calcium + 0.8(4-albumin)
normal calcium levels?
8.5 - 10 mg/dL
what levels of corrected calcium is mild, moderate, or severe
mild: <12
moderate: 12 - 14
Severe: > 14
HCM treatment algorithim:
if less than 12
for mild sxs:
for moderate sxs:
mild: drink 3L/day - repeat Ca level in 4 weeks; d/c meds that increase Ca2+
moderate: consider alternate cause; give hydration (200 - 400 mL/hr 0.9% NS) and bisphosphonate (may repeat 7 days after if needed)
HCM treatment algorithim:
if greater than 12
no life threatening symptoms or severe symptoms
either one is treated the sameeeeeeee zoledronic acid 4 mg or pamidronate 60 to 90 mg can give calcitonin - but only works for 48 hours before tachyphylaxis
T or F: when treating HCM -you MUST adjust for renal dysfunction
false!
for HCM - you do not!!!
it is the Ca2+ that is causing the renal dysfunction
needs
when do you use loop diuretics for HCM pts?
if the fluids are too much and the pts get fluid overload — then use loop diuretics
what drugs can be used for REFRACTORY HCM
phosphates
gallium nitrate
denosumab
phosphates and refractory HCM:
use in caution to severe _______
may induce metastatic ______
nausea/diarrhea
hypercalcemia
induce metastatic calcification
Zoledronic acid 4 mg IV over _______ monthly (for chronic HCM)
15 minutes
Pamidronate 90 mg IV over _______ monthly (for chronic HCM)
2 - 4 hours
SREs (skeletal related events) are defined as: Pathological \_\_\_\_\_\_ need for \_\_\_\_\_\_ or \_\_\_\_\_\_ \_\_\_\_\_\_ compression Hyper\_\_\_\_\_\_\_\_
pathological FRACTURE
need for bone radiotherapy or surgery
spinal cord compression
hyperCALCEMIA
SRE morbidity and mortality:
bone pain and structural damage leads to what two things?
reduces in quality of life by limiting ______ and decreased social function
leads to radiotherapy ad bone surgery
limits mobility
treatment options of bone metastases?
goal - palliate symptoms radiation - localized chemo - systemic IV bone modifying agents radioisotopes
Women with breast cancer: fracture risk factors?
bone mineral density Aromatase inhibitor treatment Age (> 65 y.o) corticosteroid use ( > 6 mos) BMI < 20 kg/m2 family hx of hip fracture hx of fracture before age 50 smoking
Men with prostate cancer: fracture risk factors?
androgen deprivation therapy
Radiation therapy works well and acts (slow or fast)
slow! 1 - 2 weeks for pain relief
great response rate tho
IV bisphosphonates for SRE:
options?
Pamidronate 90 mg IV over 2 - 4 hours q 3 -4 weeks
or
Zoledronic acid 4 mg IV over 15 minutes every 3 - 4 weeks
(RENAL DOSE ADJUST, YO!)
when treating SREs with bisphosphonates what is good contaminant therapy?
supplmentation of calcium 500 mg and vit. d 400 IU bid!!!
denosumab - has approved indications for what?
bone metastases from solid tumors (Xgeva q4wks)
osteopenia from breast cancer (prolia Q6mos)
and now indicated for hypercalcemia of malignancy when refractory to bisphosphonate therapy
denosumab:
should have _____ corrected prior to initiation
supplement: _________
yay or nay - renal dosage adjustments in package insert?
Very $$$$
correct hypocalcemia
supplement calcium 1000 mg and vit D QD
no renal dosage
V bad ADE of denosumab and bisphosphonates?
OSTEONECROSIS of the jaw!! (ONJ)
what makes osteonecrosis occur at a higher risk?
IV or PO
and
Monthly or yearly agent
IV is worse
monthly is worse
what makes osteonecrosis occur at a higher risk? which drugs are worse?? pamidronate denosumab zoledronic acid
zoledronic acid and denosumab are worse
possible causes of ONJ
invasive dental procedures
poor oral hygiene
use of dental appliances
(do dental procedure before these agents if you can!!)
Renal Dysfunction and bone drugs
rank the drugs from most to least affect on kidneys
zoledronic acid > pamidronate»_space; denosumab
Renal Dysfunction and bone drugs
Bisphosphonate should not be used if CrCl < _____ or pts taking ______ meds
< 30 mL/min
nephrotoxic meds
Renal Dysfunction and bone drugs
Denosumab:
renally eliminated - yes or no
no!
common ADEs of the bone drugs
hypocalemia!! (bigger in denosumab) bone pain Nausea diarrhea fatigue
Colorectal Cancer: Risk Factors ---- Age Family Hx of Colon cancer Dietary: \_\_\_\_ fat and \_\_\_\_ fiber \_\_\_\_: small % will turn into cancer
high fat/low fiber
polyps
Colorectal Cancer:
what are the two hereditary syndromes?
FAP (familial adenomatous polyposis)
HNPCC (hereditary nonpolyposis colorectal cancer)
If pt has FAP - start screening for colon cancer at age _____
10 - 12!
If pt has HNPCC - start screening for colon cancer at age _____
20 - 25
if pt has family hx of colon cancer - start screening at age ____
40 or 10 years before when family member had diagnosis
General age to start getting colon cancer screenings?
45
50 y.o FOR SURE
common screening for colon cancer is _____ and is done every ______
colonoscopy every 10 years
Colorectal Cancer:
what are some lifestyle things that are risk factors
alcohol
smoking
obesity
Screening tests for Colorectal Cancer:
Which ones primarily detect cancer only?
FOBT (fecal occult blood test)
FIT (fecal immunohistochemical test)
Screening tests for Colorectal Cancer:
which ones can detect cancer and advanced lesions
Endoscopic and radiologic exams
Screening tests for Colorectal Cancer:
How to avoid false positives with FOBT?
avoid red meat and raw veggies with peroxidase activity (turnips, broccoli, cauliflower, and radishes)
3 DAYS PRIOR TO TESTING
Screening tests for Colorectal Cancer:
How to avoid false negatives with FOBT?
Avoid vitamin C in excess for 3 days prior to testing
Screening tests for Colorectal Cancer:
Medical restrictions for FOBT? (good counseling points!)
Avoid enemas/rectal meds for 3 days prior
avoid ASA/NSAID for up to 7 DAYS prior
avoid testing if blood from hemorrhoids is present
Delay testing until 3 days after menstrual bleeding has ended
Which endoscopy procedure is the gold standard for detecting colon cancer and why
colonoscopy! bc it can see the entire bowel
flexible sigmoidoscopy lets you only 60% of the bowel
What is an important mutation to detect during the work up of colorectal cancer?
dMMR - defective mismatch repair
will influence which kind of chemo can be used!!!
If a pt has dMMR or MSI-H and has stage II disease - what does that mean?
do NOT use adjuvant 5-FU because it predicts a decreased benefit!
If a pt has dMMR or MSI-H and has stage III disease - what does that mean?
use adjuvant 5-FU they will have benefit from that therapy!
pMMR vs dMMR?
p = proficient d = defective
what is the preferred chemo adjuvant therapy in colorectal cancer?
FOLFOX
5-FU, leucovorin, oxaplatin
what does FOLFIRI chemo consist of?
5-FU, leucovorin, irinotecan
A _____ deficiency will lead to increase toxicities in 5-Fu
DPD
mutations/deficiencies in _____ will lead to toxicities of irinotecan
UGT1A1
Irinotecan ADE’s:
early or late onset _______
could be fatal….
diarrhea
Irinotecan can have _______ syndrome - should be treated with _____
cholinergic
atropine
what drug has an unique toxicity of cold intolerance and the sensation of not being able to breathe
(they can breathe just feel that way)
oxaliplatin
seen in FOLFOX for colorectal!!
what drug has an unique dose limiting toxicity of hand-foot syndrome
capecitabine (5- Fu prodrug)
what are some antibody drugs to use in colorectal cancer - and what are the targets?
Cetuximab - EGFR
Bevacizumab - VEGF
Panitumumab - EGFR
cannot use cetuximab and panitumumab for colorectal cancer if the pt is ________
pt is KRAS mutant
pt MUST be KRAS wild to use these drugs
Significant toxicities of bevacizumab?
HTN! and bleeding
