Oncology 5 Flashcards
What is a barrier to delivery of curative doses of chemotherapy?
toxicity
-prevention/treatment strategies are available to assist in managing toxicity
-proper assessment prior to the initiation of chemotherapy and between tx cycles is important
-can often detect toxicities and tx which may prevent possible organ damage, improve QoL and allow tx to continue
What are the facts regarding chemotherapy-induced toxicity?
most patients experience side effects
for most patients, side effects can be controlled
many effective drugs and preventative measures can reduce or eliminate side effects
Why is it important to manage the side effects of chemotherapy?
reduce anxiety
improve QoL
maintain optimal chemo dose and schedule
True or false: chemotherapy has a wide therapeutic index
false
chemotherapy has a narrow therapeutic index
What is the common mechanism of cytotoxic drugs?
attack dividing (growing) cancer cells
-lack of specificity - attacks rapidly dividing cells
-damage occurs to healthy cells that have rapid turnover
What are the side effects of chemotherapy a result of?
damage to healthy cells
-bone marrow, GI epithelium, hair follicles and gonads
What are the benefits and risks of using two or more agents?
two or more agents have greater response than when used alone
also greater toxicity risk
Describe the average timelines of chemotherapy-induced toxicities.
nausea/vomiting: day 1-3/4
fatigue: day ~4 onward
mouth sores: day 5-~12
neutropenia: day ~7-20
hair loss: day 15 onward
Differentiate urgent, short term, and long term adverse effects.
urgent:
-need to contact cancer clinic/health care team immediately
short term:
-occur during treatment, can often be managed with symptomatic care strategies or dose adjustments
long term:
-may occur months-years after treatment stopped, recognition and treatment can be more difficutlt
What are examples of urgent adverse events?
temperature
shivering
flu symptoms
nose or gum bleeding that doesnt stop
mouth sores that prevent eating/drinking
uncontrolled vomiting or diarrhea
difficulty breathing
chest pain/irregular heart rhythm
decreased urination/dark urine
anaphylaxis
What are the short term adverse effects of chemotherapy?
NVDC
mucositis/stomatitis
myelosuppression
hair growth alterations
wt gain/loss
taste/smell alterations
fatigue
hepatic/renal changes
cardiac function changes
rash/skin/nail changes
hypertension
What are the long term side effects of chemotherapy?
infertility
secondary malignancies
heart failure
osteoporosis
pulmonary fibrosis
cataracts
peripheral neuropathy
hearing loss
fatigue
endocrine abnormalities
What is used to grade chemotherapy adverse events?
Common Terminology Criteria for Adverse Events (CTCAE)
-describes the severity of toxicity for pts receiving cancer therapy
What are the different chemotherapy toxicity grades?
grade 0: none
grade 1: mild
grade 2: moderate
grade 3: severe
grade 4: life threatening
grade 5: death
Describe the different grades of stomatitis.
0-1:
-painless ulcers, erythema or mild soreness
2:
-painful erythema, edema or ulcers but can eat
3:
-painful erythema, edema or ulcers and cannot eat
4:
-mucosal necrosis, requires parenteral support
Describe the different grades of diarrhea.
0-1:
-increase of 2-3 stools/day compared with usual BM
2:
-increase of 4-6 stools/day compared with usual BM or stools during night
3:
-increase of 7-9 stools/day compared with usual BM or unable to digest food or control BMs
4:
-life threatening, 10+ stools/day or very bloody diarrhea or need for IV fluids
Describe the different grades of nausea and vomiting.
0-1:
-1 episodes/day but can eat
2:
-2-5 episodes/day; intake decreased but can eat
3:
-6-10 episodes/day and cannot eat
4:
-10+ episodes/day or requires parenteral support; dehydration
What are the symptoms seen with hypersensitivity reactions?
local reactions:
-rash, urticaria, erythema, phlebitis, pain and vein discoloration
systemic reactions:
-bronchospasm, angioedema, hypotension, rash, pruritis, dermatitis
includes infusion-related rxns (no allergic component)
What is often used to prevent infusion-related reactions?
steroid
H2RA
antihistamine
acetaminophen
Which drugs are most commonly associated with hypersensitivity reactions?
taxanes
platinums
bleomycin
monoclonal antibodies
What are the hematological toxicities of chemotherapy?
myelosuppression
-neutropenia, thrombocytopenia, anemia
What is the primary dose-limiting toxicity of chemotherapy?
myelosuppression
How does chemotherapy cause hematological toxicity?
direct cytotoxic effects on the myeloid stem cells by reducing bone marrow production and total circulating blood cells
-indirectly affects the hematopoietic system by altering the bone marrows microenvironment and interacting with lymphoid cells
True or false: hematological toxicity of chemotherapy is irreversible
false
generally reversible but can lead to severe complications requiring hospitalization and dose delays and/or dose reductions
What are the main cell lines from bone marrow impacted by chemotherapy?
red blood cells
-anemia
white blood cells
-neutropenia
platelets
-thrombocytopenia
What is the nadir period?
lowest point for blood cell count
What are AND decrease and nadir duration dependent upon?
therapy
dose
route of administration
recovery period also dependent on regimen and patient status
What are the symptoms of anemia?
fatigue
weakness
lightheadedness
dyspnea
What is the management of chemotherapy-induced anemia?
infusion of packed RBCs
Which agents are not recommended for management of chemotherapy-induced anemia?
ESAs
Differentiate the different grades of chemotherapy-induced anemia.
grade 1: HgB LLN - 100 g/L
grade 2: HgB 100-80 g/L
grade 3: HgB < 80 g/L, transfusion needed
grade 4: life-threatening, urgent care
grade 5: death
What does chemotherapy-induced thrombocytopenia put patients at risk of?
bleeding
What is the management of chemotherapy-induced thrombocytopenia?
dose adjustments, treatment delays, and/or platelet transfusion
Differentiate the grades of chemotherapy-induced thrombocytopenia.
grade 1: < LLN - 75 x 10e9/L
grade 2: < 75-50 x 10e9/L
grade 3: <50-25 x10e9/L
grade 4: <25 x10e9/L
True or false: chemotherapy-induced neutropenia is unpredictable and irreversible
false
predictable and reversible
What composes the ANC?
total # of neutrophils + the bands
What is neutropenia?
ANC less than 1.5 cells x 10e9/L
What is the management of chemotherapy-induced neutropenia?
dose reduction or treatment delay, prophylaxis with GCSFs
Differentiate the different grades of chemotherapy-induced neutropenia.
grade 1: < LLN -1.5 x 10e9/L
grade 2: 1.5-1.0 x 10e9/L
grade 3: 1.0-0.5 x 10e9/L
grade 4: < 0.5 x10e9/L
What defines febrile neutropenia?
neutrophils:
- < 0.5 or < 1.0 with a predicted decline to < 0.5 within 48 hours
fever:
-single temperature of > 38.3 C or a temperature of > 38 C sustained for over one hour
What are the risk factors for febrile neutropenia?
cytotoxic agent
dose intensity of the regimen
concomitant chemoradiation therapy
severity and duration of neutropenia
patient factors
What is the urgency of febrile neutropenia?
medical emergency
-seek medical attention immediately
What should chemotherapy patients be advised not to do when they have a fever?
do not take acetaminophen, ibuprofen or ASA until have contacted a HCP
How is febrile neutropenia treated?
empirically with broad spectrum antibiotics
-monotherapy with anti-pseudomonal beta-lactam (pip/taz, cefepime, meropenem, ceftazidime)
-vancomycin (or linezolid) if high suspicion of gram + involvement
When should we suspect gram-positive involvement in febrile neutropenia
known MRSA carrier or past infection
catheter-related infection
SSTI, severe mucositis
hemodynamically unstable or sepsis
Describe proper infection prevention for chemotherapy patients.
good hygiene - wash hands frequently
protect your skin
-avoid cuts/scrapes, clean wounds
-use sunscreen
reduce exposure
-avoid crowded places and contact with sick ppl
-avoid sharing food, dishes and personal items
good mouth care
care of medical devices
What are examples of GCSFs?
filgrastim
pegfilgrastim (longer acting)
Differentiate primary and secondary prophylaxis with GCSFs.
primary prophylaxis:
-used empirically for pts at greater than or equal to 20% risk for febrile neutropenia
secondary prophylaxis:
-prevent recurrence after experiencing febrile neutropenia
-to shorten duration of severe neutropenia in pts who experienced neutropenia without fever prev
What is the MOA of GCSFs?
regulates release, promotes promotes proliferation and differentiation of myeloid cells, including neutrophils
What are the GI chemotherapy toxicities due to?
rapid turnover of the epithelial lining of the GIT
When does mucositis usually present?
during the neutrophil nadir (7-10 days with cytotoxics) when the immune system is most vulnerable
What are the risk factors for GI chemotherapy toxicities?
continuous chemotherapy infusions
concurrent radiation therapy
What are the consequences of mucositis?
painful
limited nutritional intake
affect outcome (dose reduction, delay, or stop)
potential site for infection
What are the prevention strategies for mucositis?
good oral hygiene
-soft toothbrush, gentle flossing, moisture rinses
-avoid irritating foods
-make sure dentures fit
salt/baking soda/normal saline rinse
-rinse 3-4 times daily
-avoid alcohol containing mouthwash
ice chips
-chewing 30 min prior to chemo may help
-CI with some chemo regimens
What are the potential treatments for chemotherapy-induced mucositis?
prescription mouth wash
-steroids, local anesthetics, topical analgesics
fungal infection
-nystatin, oral fluconazole
analgesia
severe symptoms
-hospitalization, IV narcs, parenteral nutrition
Which mouthwashes are not recommended for chemotherapy-induced mucositis? Why?
Koolstat or Magic Mouthwash
-not evidence based and ineffective for treating oral thrush and pain
-expensive for pt and the system
-risk of nystatin resistance
-risk of steroid causing oral thrush
-risk of causing harm to pts
What causes chemotherapy-induced dyspepsia/heartburn?
direct insult to cells of GIT
often a side effect of supportive care medications
patient stress
difficult to distinguish between nausea and heartburn
-but heartburn can worsen nausea
How is chemotherapy-induced dyspepsia/heartburn managed?
avoid aggravating factors
H2RA, PPI, antacid
What is the risk of prolonged or severe chemotherapy-induced diarrhea?
dehydration
Describe the non-pharm management of chemotherapy-induced diarrhea.
small, frequent meals, frequent hydration
limit caffeine, fried, greasy foods, foods high in lactose or sorbitol
avoid foods high in insoluble fiber
encourage foods high in soluble fiber
avoid excess hyperosmotic liquids
How is chemotherapy-induced diarrhea managed?
rule out infectious causes
loperamide or diphenoxylate
octreotide
What is the MOA of loperamide and diphenoxylate?
opioid analogues, reduce gut motility, reduce fluid secretion
What is the MOA of octreotide?
somatostatin analogue
-reduces fluid secretion from stomach and intestine
-increases fluid reabsorption from intestine
Which chemotherapy regimen commonly causes diarrhea?
irinotecan
Differentiate acute and delayed irinotecan-induced diarrhea?
acute diarrhea
-occurs within 24h
-51% pts, 8% severe
-cholinergic mechanism
delayed diarrhea
-more than 24h after admin at any time
-88% pts, 31% severe
-secretory diarrhea
-may be life-threatening
How is acute irinotecan-induced diarrhea managed?
atropine
Describe the loperamide regimen for irinotecan-induced diarrhea.
intensive loperamide regimen
-4 mg at first onset of diarrhea
-followed by 2mg scheduled every 2h during the day
-during the night, 4mg every 4h
-take until diarrhea free for 12h
-seek medical attention if no resolution within 24h
What are the many contributors to constipation in cancer patients?
supportive care tx side effects
chemo-induced
-reduction in GI motility
-more H20 reabsorbed from GIT
radiation to GIT
What are the consequences of constipation in cancer patients?
pain and discomfort
increased nausea
bowel obstruction
hospitalization
Describe non-pharm management for chemotherapy induced constipation.
increase fluid intake (1.5-2L)
physical activity as tolerated
promote fiber intake
minimize alcohol and caffeine intake
What are the management options for chemotherapy-induced constipation?
stimulants (onset 6-12h)
-senna, bisacodyl
osmotic (onset 1-3 days)
-lactulose, PEG
enemas, suppositories
-3rd line
What are some warning signs with constipation?
no BM for 3-5 days
not passing gas
blood in stool (or tarry stools)
foul smelling vomit
What might occur to taste and smell in chemotherapy patients?
alterations in taste and smell
-often described as a metallic or chemical taste
-may lead to reduced appetite & wt loss
-may affect taste by direct taste receptor stimulation due to secretion of the drug in saliva or via gingival crevice fluid
-taste changes may persist after drug clearance due to damage to taste buds and psych effects
What are some cutaneous reactions to chemotherapy?
photosensitivity
-exaggereated by UV light; sunburn; blistering
-minimize sun exposure; use SPF15 or greater
nail changes
hyperpigmentation
dry skin, rashes
Which chemotherapy agent is hand foot skin reaction commonly encountered with?
capecitabine
-also liposomal doxorubicin, continuous 5-FU infusions, everolimus, lapatinib
When doess the hand foot skin reaction usually appear?
first few cycles of therapy
What does the hand foot skin reaction correlate to?
correlation with treatment response
-capecitabine in metastatic breast cancer pts
What is the treatment for HFS?
prevention is key - NO treatment
What are the prevention strategies for HFS?
avoid exposure to heat
-wash dishes in luke warm water
-avoid prolonged hot baths or showers
protective gloves and socks
moisturizes to hands and feet BID
avoid activities that apply pressure to skin of hands and feet
avoid fragrances
What are the hair changes that might be seen with chemotherapy?
alopecia
depigmentation
change of colour
change of texture
eyelash and eyebrow changes
Where is hair loss most common with chemotherapy?
scalp
-this hair grows most rapidly
Which cytotoxic agents commonly cause hair loss?
doxorubicin (anthracycline)
-up to 100%, onset days-wks
-regrowth 2-3 mo after d/c
paclitaxel (taxane)
-up to 93%
-onset 14-21days, can be sudden
-total body hair loss
docetaxel
-reports of irreversible hair loss
Which agents have a low risk for hair loss?
5-FU
capecitabine
FOLFOX
FOLFIRI
CMF
many oral targeted agents
Which chemotherapy agents often caused neurotoxicity?
platinum agents
taxanes
vinca alkaloids
proteasome inhibitors
immunomodulating agents
How does chemotherapy-induced neurotoxicity present?
most common: peripheral neuropathy
ototoxcitiy: tinnitus, hearing loss
autonomic neuropathies
What is the treatment for chemotherapy-induced peripheral neuropathy?
antidepressants
anticonvulsants
opioids
What can increase the risk of chemotherapy-induced cardiotoxicity?
risk is greater if there is a known history of heart disease
-arrhythmia
-myocardial necrosis
-angina or MI
-pericardial disease
Which agents can cause cardiotoxicity?
anthracyclines
fluorouracil
trastuzumab
How do anthracyclines cause cardiotoxicity?
direct injury to heart, either acutely or in a delayed or chronic fashion
-MOA: reactive free radical formation causing damage to myocardial cells
dose dependent = lifetime maximum doses
What kind of monitoring is required with anthracyclines/
baseline cardiac function (ECHO or MUGA) and routine monitoring
What is the second most common cause of chemotherapy-related cardiotoxicity?
fluorouracil
-after anthracyclines
What kind of cardiotoxic effects is trastuzumab associated with?
decreased LVEF
CHF
arrhythmias
HTN
cardiomyopathy
When is trastuzumab associated cardiotoxicity more pronounced?
if given concurrently with an anthracycline
-not recommended
How is trastuzumab associated cardiotoxicity managed?
reversible with d/c and initiation of standard cardic medications
