Term
| common complications of chemotherapy |
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Definition
nausea/vomiting
myelosuppression: neutropenia, anemia, thrombocytopenia
mucositis: stomatitis, diarrhea
hepatotoxicity
neuropathies
alopecia
infertility
onc emergencies: tumor lysis, hypercalcemia, SVC syndrome, spinal cord compression |
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Term
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Definition
anemia: erythropoiesis stimulating agents (should not treat patients with ESAs with the intent to cure their cancer), blood transfusions
thrombocytopenia: platelet transfusions; platelet count less than 10 the patient should get a transfusion (this is the threshold for life threatening bleeding)
leukopenia (neutropenia): colony stimulating factors; just concerned about neutrophils b/c these are the first line defense |
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Term
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Definition
prevention with CSFs indicated if neutropenic fever risk is at least 20%
start day after chemo and continue until neutropenia resolves
G-CSF (granulocyte colony stimulating factor) = sargramostim
GM-CSF (granulocyte/macrophage colony stimulating factor): filgrastim
stimulate bone marrow to produce white blood cells
[image]
WBC count drops dramatically during chemotherapy
nadir = low point in WBC count
with CSF:
the nadir doesn't drop as low and there is faster recovery
risk of development of infection is much less
filgrastim:
daily
SQ
pegfilgrastim:
once
SQ
sargramostim:
daily
IV over 2 hours or SQ
ADRs: headache, bone pain, pain at injection site, fever (sargramostim)
primary ADRs of these drugs is bone pain (long bones) b/c marrow is stimulated |
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Term
| chemotherapy induced nausea and vomiting (CINV) |
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Definition
incidence of chemomtherapy induced nausea and vomiting: 70-80% of all cancer patients
negative impact on quality of life: poor compliance
complications: metabolic imbalances, dehydration, nutrient depletion, anorexia, esophageal tears |
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Term
| types of nausea and vomiting |
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Definition
[image]
majority of N/V is acute (within 24 hours of chemo administration)
after 24 hours it is delayed N/V
anticipatory nausea and vomiting:
originate in the cerebral cortex
learned response from prior therapy
best therapy is PREVENTION of emesis during treatment
delayed nausea and vomiting:
originates in the GI tract?
mechanism is largely unknown (NK1 - substance P receptor)
chemotherapy implications: cisplatin, cyclophosphamide, carboplatin |
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Term
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Definition
afferent impulses to vomiting center (VC) received from:
chemoreceptor trigger zone (CTZ)
gastrointestinal tract
cerebral cortex
nucleus tracts solitaries (NTS)
vomiting occurs when efferent impulses are sent from VC to involved organs
signals coming out from the VC are DOPAMINE MEDIATED - IMPORTANT when treating someone who is actively nauseous
5HT3 is an INCOMING signal - inhibited by ondansetron
prochlorperazine (a phenothiazine) is a dopamine receptor inhibitor - outgoing signal shut off = good for active nausea |
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Term
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Definition
specific chemotherapeutic agents
dose: higher dose = more N/V
schedule
route of administration: medication given orally with direct GI irritating qualities
patient specific risk factors:
young age
female
no alcohol history
prior N/V with chemotherapy
concurrent radiation
history of N/V with pregnancy
motion sickness |
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Term
| principles of emesis control |
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Definition
stop it before it happens
use lowest maximally effective dose prior to chemotherapy
consider side effects of antiemetics
tailor the regiment to the patient
delayed emesis is a major problem
don't be a hero
PREVENTION is the most important for chemo induced N/V |
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Term
| emetogenicity of chemotherapy |
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Definition
based on percentage of patients that will get sick if given placebo
minimal: <10%
low: 10-30%
moderate: 30-90%
high: >90% |
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Term
| combination chemotherapy: how do you determine an antiemetic regimen for combination therapy? |
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Definition
just use the highest level agent
example:
CHOP for non-Hodgkin's lymphoma
cyclophosphammide = moderate
doxorubicin = moderate
vincristine = minimal
prednisone = minimal
overall = MODERATE |
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Term
| pharmacologic agents for CINV |
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Definition
D2 antagonists: phenothiazines, butyrophenones, substituted benzamides
corticosteroids
5HT3 antagonists
cannabinoids
NK1 antagonist |
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Term
| non-pharm options for CINV |
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Definition
behavioral therapy
relaxation techniques
acupuncture?
helps with anticipatory N/V |
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Term
| 5HT3 receptor antagonists |
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Definition
ondansetron, granisetron, dolasetron, palonosetron
MOA: inhibition of 5HT3 receptors on vagal afferent neurons in GI and in CTZ
effect against ACUTE N/V with moderate to high ematogenic potential
efficacy improved when used with a steroid (dexamethasone)
well tolerated, minimal side effects (headache, constipation)
expensive
used to PREVENT CINV (acute)
no real difference among drugs in the class
ondansetron is generic
palonosetron: IV only; 40 hour t1/2; data on delayed CINV; 2nd line after ondansetron |
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Term
| NK1 antagonist - aprepitant |
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Definition
MOA: block neurokinin receptor
1st new drug effective for DELAYED NAUSEA
adds efficacy for acute CINV
well tolerated, minimal side effects
significant CYP450 DIs (3A4 inhibitor)
very expensive
used to PREVENT CINV (ACUTE AND DELAYED) |
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Term
| prevention of anticipatory emesis |
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Definition
learned response from prior therapy
best therapy is prevention of emesis during chemotherapy
relaxation techniques shown to be effective
benzodiazepines: lorazepam beginning prior to chemotherapy or triggering event (not an anti-emetic, just relaxes the patient) |
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Term
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Definition
treatment should be chosen base on:
chemotherapy regimen's emagogenic potential - generally guides therapy
patient history of: alcohol intake, motion sickness, prior responses to antiemetics, age, concurrent radiation, sickness with pregnancy
CHEMOTHERAPY NAIVE (CYCLE 1):
EP Level: Minimal
no prophylaxis
PRN D2 blocker, dronabinol
EP Level: Low
1 drug, preferred drug is a corticosteroid
scheduled D2 blocker, STEROID, dronabinol
ex) compazine OR dexamethasone
EP Level: Moderate
2 drugs
scheduled 5HT3 receptor blocker and steroid
ex) dexamethasone + granisetron
EP Level: High
3 drugs
scheduled 5HT3 receptor blocker, steroid, NK1 antagonist
ex) dexamethasone, dolasetron, aprepitant |
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Term
| prevention of delayed emesis |
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Definition
chemotherapy implicated: cisplatin, cyclophosphamide, carboplatin, high dose doxorubicin
mechanism is largely unknown (NK1)
options:
NK1 antagonist
dexamethasone
high dose metoclopramide - risk of tardive dyskinesia
prochlorperazine
traditional 5HT3 receptor antagonists are INEFFECTIVE
NK1 antagonist is the gold standard for delayed emesis
aprepitant: BEWARE OF DRUG INTERACTIONS (paclitaxel, docetaxel) |
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Term
| prevention of cycle 2 and beyond |
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Definition
complete or major responders: continue same antiemetics
partial responders or failures:
patients not receiving a 5HT3 antagonist add 5HT3 antagonist + steroid
if got 5HT3 but not aprepitant, add aprepitant
if got triple drug (steroid + 5HT3 + aprepitant) try to change to different 5HT3 |
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Term
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Definition
refractory = active N/V
5HT3s HAVE NOT BEEN PROVEN EFFECTIVE TO TREAT CINV
most used agents are active on dopamine
no sequence to use (phenothiazines USUALLY first)
options:
phenothiazines: prochloroperazine, promethazine
butyrophenones: haloperidol, droperidol
substituted benzamide: metoclopramide
cannabinoid: dronabinol
blocking outgoing dopamine signal will help the quickest |
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Term
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Definition
rapid destruction of cancer cells
results in release of intracellular contents/metabolites
products overwhelm normal clearance
[image]
complications:
hyperuricemia
hyperphosphatemia
hyperkalemia
hypocalcemmia
RENAL FAILURE |
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Term
| predisposing factors for the development of TLS |
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Definition
large tumor burden
rapid tumor growth
chemotherapeutic sensitivity
baseline renal insufficiency
increased LDH (lactate dehydrogenase): intracellular enzyme that is a marker of cell death; enzyme is released when cells die
when patients have a high baseline LDH it means the tumor is so large it is dying on its own
acute leukemias are the highest risk for developmening TLS: many cancer cells, fast growing, and sensitive to chemotherapy |
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Term
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Definition
hyperkalemia: arrhythmias, muscular weakness and cramping, N/V/D
hyperphosphatemia: renal insufficiency
hypocalcemia: arrhythmias, muscle cramping and spasm, mental status changes, seizures
hyperuricemia: N/V/D, renal insufficency
hyperuricemia is > 4 |
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Term
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Definition
avoid drugs that can increase uric acid: aspirin, thiazides, probenecid, pyrazinammide, ethambutol
ALLOPURINOL
HYDRATION
urine alkalinization:
bicarb fluids
acetazolamide
diuretics (loop) - flush out the kidneys |
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Term
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Definition
treat electrolyte disturbances same as you would in non-oncology patients
hyperuricemia is different from gout! (gout is slow accumulation of uric acid) |
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Term
| management of hyperuricemmia |
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Definition
prevention of urate nephropathy
allopurinol - decrease the production of urice acid, but will not do anything for uric acid that is already there
rasburicase - recombinant enzyme that breaks down the uric acid that is already there
avoid drugs that increase uric acid: aspirin, thiazides, probenecid, pyrazinamide, ethambutol |
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Term
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Definition
alkalinizaiton of urine - uric acid stays in a more soluble state
bicarbonate fluids
DO NOT MAKE YOUR FLUIDS HYPERTONIC
normal saline = 154 mEq/L of NaCl, this is your max concentration
how much Na bicarb can you add to 1 L of:
NS - already at max concentration, cannot add more sodium bicarb
D5W - doesn't have any sodium in it, so you can add up to 154 mEq (standard it to round it off to 150 mEq)
D5W1/2NS - is half concentration of NaCl (77mEq) so can add up to 77 more mEq of Na bicarb (77 mEq usually rounded to 75 mEq)
when bicarb fluids are not enough - acetazolamide
carbonic anhydrase pumps protons into the urine, if this is shut off by acetazolamide it will increase the urine pH |
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Term
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Definition
prevent uric acid production
inhibit xanthine oxidase
DOES NOT DECREASE ALREADY PRESENT URIC ACID |
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Term
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Definition
catalyzes breakdown of uric acid to allantoin and hydrogen peroxide
not present in humans
non-recombinant form has a high incidence of hypersensitivity
RASBURICASE:
injectable formulation of urate oxidase
FDA approved for: "the inital management of plasma uric acid levels in pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid"
uric acid is high and chemo will increase uric acid further - use rasburicase
DO NOT GIVE RASBURICASE AS A BOLUS INJECTION
rasburicase is very effective at clearing out uric acid; usually patients get one dose of rasburicase (gets rid of the uric acid that is there) and the patient is then given allopurinol to prevent the formation of uric acid
rasburicase BBW - anaphylaxis, hemolysis, and methemoglobinemia
give chemotherapy 4-24 hours after giving rasburicase |
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Term
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Definition
for life-threatening electrolyte disturbances
refractory to other therapies |
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Term
| hypercalcemia of malignancy |
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Definition
most common metabolic emergency - 10-30% of all cancer patients
most common with: lung cancer, breast cancer, hematologic malignancies (multiple myeloma, lymphoma), genitourinary malignancy
tumors produce a parathyroid like hormone
destruction of the bone through metastasis can lead to hypercalcemia
etiology:
increased bone resorption = most important cause
local osteoclast hypercalcemia - involves area around malignancy; mediators = cytokines, chemokines
humoral hypercalcemia - bone metastasis absent or minimal; primarily mediated through tumor production of PTHrp
inadequate renal compensation - often due to PTHrp
increased intestinal calcium absorption - uncommon mechanism, some lymphoma patients; due to increased productio of calcitonin by tumor tissue
doesn't matter where it's coming from, it will be treated the same |
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Term
| hypercalcemia signs and symptoms |
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Definition
renal: nephro-calcinosis, dehydration, polyuria
GI: N/V, anorexia, constipation, pancreatitis
neuro: mental status changes, confusion, stupor, seizure, coma, muscle weakness
cardiac: shortened QT, wide T wave, arrhythmia
other: bone pain, puritisi, hypophosphatemia, fatigue |
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Term
| diagnosis of hypercalcemia |
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Definition
history and PE
bone scan or skeletal survey
lab findings:
elevated total serum calcium or ionized calcium
low or undetectable immunoreactive parathyroid hormone (iPTH)
inorganic phosphorous low to normal
1,25-dihydroxyvitamin D low to normal |
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Term
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Definition
mild: corrected calcium < 12 mg/dL
moderate: corrected calcium 12-14 mg/dL
severe: corrected calcium > 14 mg/dL
normal calcium: 8.5-10.5 mg/dL
CORRECTED CALCIUM = MEASURED CALCIUM + 0.8 (4-ALBUMIN) |
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Term
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Definition
ultimate management: therapy for cancer
acute management based on degree of hypercalcemia and symptoms
MILD HYPERCALCEMIA:
asymptomatic: encourage fluid intake; discontinue drugs that increase serum calcium or decrease renal blood flow
symptomatic:
R/O other causes
hydration: NS 200-400 mL/hr - corrects dehydration, dilutes calcium and promotes renal calcium excretion
zoledronic acid 4 mg IV over 15 minutes or pamidronate 30-90 mg IV over 2-24 hours
MODERATE TO SEVERE HYPERCALCEMIA:
hydration:
hyperhydration and forced diuresis (loop diuretics)
decrease Ca by 1.6-2.4 mg/dL
onset 12-24 hours
concern: fluid overload, electrolyte abnormalities
use: decrease calcium in 1st couple of days while waiting for bisphosphonate effect
ZOLEDRONIC ACID 4 MG IV OVER 15 MIN or pamidronate 60-90 mg IV over 2-24 hours
calcitonin
rapid decrease of calcium of clinical benefit (severe symptoms or very high calcium)
bridge therapy while waiting for bisphosphonate effect
saline and loop diuretics will drop the calcium the fastest
after fluids and loops; use calcitonin (works faster than IV bisphosphonates)
after calcitonin will give zoledronic acid or pamidronate
follow up after initial evaluation:
evaluate after 48 hours
if calcium WNL: DC home
if Ca still elevated and patient symptomatic: maintain hydration and repeat Ca at day 5
evaluation on day 5-7:
if Ca WNL: DC home
if high, repeat zoledonric acid or pamidronate, and repeat 48 hours and day 5-7 monitoring plan
IV bisphosphonates will start to work in 3 days
peak activity of IV bisphosphonate is 7 days = maximum benefit
do not repeat an IV bisphosphonate until 7 days
if Ca remains high after 2nd dose of a bisphosphonate...
consider 2nd line agent:
corticosteroids
plicamycin
phosphonates
gallium nitrate |
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Term
| chronic hypercalcemia of malignancy |
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Definition
pamidronate 90 mg IV over 2-24 hours every 3 weeks
zoledronic acid 4 mg IV over 15 min monthly |
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Term
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Definition
most patients are extremely dehydrated
MOA: increase renal blood flow and enhance calcium excretion
onset of action: 12-24 hours
decreased serum calcium: 0.5-2 mg/dL |
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Term
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Definition
MOA: diuretic induced natriuresis should enhance urinary calcium excretion
may prevent hypervolemia
dosage based on patient's renal function and dosed to maintain UOP
furosemide IV initiated after NS
monitor to avoid over diuresis or hypokalemia |
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Term
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Definition
pamidronate and zoledronic acid
MOA: inhibit bone resorption, inhibit osteoclasts and activation by cytokines, inhibit recruitment and differentiation of osteoclast precursors
poor bioavailability
onset of action: 2-3 days, peak 5-7 days
may repeat in 7 days if not enough decrease seen
duration of response: 3-4 weeks
AE: fever, mild hypocalcemia, hypomagnesemia, nephrotoxicity, osteonecrosis |
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Term
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Definition
MOA: inhibits bone degradation by osteoclasts
onset of action: 1-4 hours
peak effect: 4-6 hours
duration: 72 hours
tachyphylaxis develops
decrease serum Ca: 1-2 mg/dL
if given at the same time as bisphosphonates it will stop working when the bisphosphonates will start working |
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Term
| example timeline for severe hypercalcemia management |
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Definition
[image]
start IV bisphosphonate and calcitonin at the same time to bridge therapy |
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