Lecture 9 - Supportive Care I Flashcards
Chemotherapy induced nausea vomiting
one of the most feared complications of chemotherapy despite its limited nature
complications can include: dehydration, electrolyte abnormalities, fatigue, depression
can result in inability to deliver the intended full dose of chemo especially in pts receiving highly emetogenic regimens
Types of nausea/vomiting
anticipatory
acute
delayed
breakthrough
refactory
Anticipatory
anticipating the nausea you might experience
learned response conditioned by severity and duration of previous emetic reactions from pior cycles of chemo
non-pharmacologic approaches such as hypnosis have been successful
can be provoked by sight, sound, or smell
Acute
emetic response correlating with the administration of chemo
usually within 24 hours of receiving chemo
Delayed
related to chemo occurring > 24 hours following completion of chemo
mechanism not fully understood, but there is an increased evidence that substance P binding to neurokinin 1 receptor may play a role
Breakthrough
nausea/vomiting that occurs even if on scheduled anti-emetics prior to chemo
Refractory
nausea/vomiting that persists despite appropriate anti-emetics
failed other therapies
CINV pathophysiology
process of acute CINV appears to begin in GI tract with cytotoxic chemo inducing damage to epithelial cells lining the GI tract
enterochromaffin cells lining the GI tract contain large stores of serotinin - serotonin released in massive quantities after exposure to chemo
chemoreceptor trigger zone stimulates vomiting center - located in nucleus tractus solitarii in medulla which stimulates emetic response
input to vomiting center from higher cortical centers, parynx, and GI tract can induce emesis
Progression of nausea/vomiting
progression to vomiting: nausea –> followed by wretching –> finally emesis
Nausea
inclination to vomit or as a feeling in the throat or epigastric region alerting an individual that vomiting is imminent
Wretching
labored movement of abdominal and thoracic muscles before vomiting
Vomiting
ejection or forced expulsion of gastric contents through mouth
Neurotransmitters implicated in CINV
dopamine
histamine
acetylcholine
serotinin
substance P - neurokinin 1 receptor antagonist
drugs we use target these neurotransmitters
Combination chemotherapy
when considering combo chemo, you need to consider the emetogenicity of the combo:
level 1 and 2 agents do not contribute to emetogenicity of the regimen
adding level 3 or 4 agents increases the emetogenicity of the combo regimen by 1 level per agent
add the diff levels together to decide on which antiemetics to use
Risk factors for CINV
women > men
younger pts > older pts
prior h/o motion sickness
previous h/o morning sickness
previous CINV tend to do worse
anxiety/high pretreatment anticipation of nausea
chronic ethanol can be protective
Treatment guidelines
prophylaxis for acute N/V is based on emetogenic potential of chemo
5-HT3 receptor antagonists may be substituted for each other; similar efficacy and toxicity; oral therapy is = in efficacy to IV
Highly emetogenic: regimen A
- NK-1 antagonist - pick 1
- steroid
- 5-HT3 antagonist - pick 1
- atypical antipsychotic
Regimen A: NK-1 antagonist
aprepitant oral
aprepitant injectable emulsion
fosaprepitant
rolapitant oral
netupitant/palonosetron
fosnetupitant/palanosetron
Regimen A: Steroid
dexamethasone
Regimen A: 5-HT3 antagonist
dolasetron
granisetron
ondansetron
palonosetron
Regimen A: Atypical antipsychotic
olanzapine
Highly emetogenic: regimen B
- atypical antipsychotic: olanzapine
- 5-HT3 antagonist: palonosetron
- steroid: dexamethasone
+/- lorazepam 0.5 mg to 2 mg PO or IV or sublingual q4-6h PRN +/- H2 blocker or proton pump inhibitor
Highly emetogenic: regimen C
- NK-1 antagonist (pick 1) - same as regimen A
- steroid - same as regimen A
- 5-HT3 antagonist (pick 1) - same as regimen A
+/- lorazepam 0.5 mg to 2 mg PO or IV or sublingual q4-6h PRN +/- H2 blocker or proton pump inhibitor
Moderately emetogenic: regimen A
- steroid: dexamethasone
- 5-HT3 antagonist (pick 1): dolasetron, granisetron, ondansetron, palonosetron
+/- lorazepam 0.5 mg to 2 mg PO or IV or sublingual q4-6h PRN +/- H2 blocker or proton pump inhibitor
Moderately emetogenic: regimen B
- olanzapine
- palonosetron
- dexamethasone
+/- lorazepam 0.5 mg to 2 mg PO or IV or sublingual q4-6h PRN +/- H2 blocker or proton pump inhibitor
Moderately emetogenic: regimen C
- NK-1 antagonist (pick 1)
- steroid
- 5-HT3 antagonist (pick 1)
Regimen C: NK-1 antagonist
aprepitant oral
aprepitant injectable emulsion
foasprepitant
rolapitant oral
netupitant/palonosetron
fosnetupitant/palonosetron
Regimen C: steroid
dexamethasone
Regimen C: 5-HT3 antagonist
dolasetron
granisetron
ondansetron
palonosetron
Low emetogenic regimens
just use 1 drug!
dexamethasone
metoclopramide - +/- diphenhydramine is EPS sx are present
prochlorperazine
5-HT3 antagonist - dolasestron, granisetron, ondansetron
+/- lorazepam 0.5 mg to 2 mg PO or IV or sublingual q4-6h PRN +/- H2 blocker or proton pump inhibitor
Breakthrough N/V
dopamine receptor antagonists: haloperidol or metoclopramide
phenothiazines: proclorperazine or promethazine
antipsychotic: olanzapine
benzodiazepines: lorazepam
cannabinoids: dronabinol or nabilone
serotonin antagonist: dolasetron, granisetron, or ondansetron
steroids: dexamethasone
anticholinergic: scopolamine
give an additional agent from a different drug class as needed
Delayed N/V
typically involves use of one of the following: dexamethasone, NK-1 antagonist, olanzapine
Anticipatory N/V
prevention - use optimal antiemetic therapy during every cycle of tx
behavioral - relaxation/systemic desensitization, hypnosis, cognitive distraction, yoga
acupuncture/acupressure
lorazepam
Other prevention guidelines: oral chemo
high to moderate emetogenic risk: start before chemo and continue daily - 5-HT3 antagonists
low to minimal emetogenic risk: start before chemo and maybe given daily or PRN - metoclopramide, prochlorperazine, 5-HT3 antagonists
Other prevention guidlines: radiation induced emesis
radiation therapy to the upper abdomen/localized sites (head, neck, GI tract) - 5-HT3 antagonists work well
total body irradiation: start pretreatment for each day of radiation therapy - granisetron PO +/- dexamethasone or ondansetron PO +/- dexamethasone
Amino acid infusion
give antiemetics 30 min prior to start of amino acid infusion: 5-HT3 antagonists, NK-1 antagonists; NOT steroids due to downregulation of somatostatin receptors
Toxicities: 5-HT3 antagonists
headache, asymptomatic and transient EKG changes, constipation, increased transaminases, QTc prolongation risk
Toxicities: corticosteroids
short term use: anxiety, euphoria, insomnia, hyperglycemia, increased appetite
Toxicities: substance P antagonists
hiccups!
worry about drug interactions
Toxicities: dopamine antagonists
extrapyramidal side effects, diarrhea, sedation
Toxicities: atypical antipsychotic
dystonic rxns, sedation
Toxicities: phenothiazines
sedation, akathesia, dystonia, IV promethazine = tissue damage
Toxicities: cannabinoids
drowsiness, dizziness, euphoria, mood changes, hallucinatinos, increased appetite
Toxicities: benzodiazepines
sedation, hypotension, urinary incontinence, hallucinations
Toxicities: anticholinergic
anti-cholinergic side effects
Anti-emetics are most effective when given
as prophylaxis
begin therapy at least 5-30 min prior to chemo
administer around the clock until chemo is complete and provide PRN agents for breakthrough N/V
always provide PRN antiemetics when pts go home
Mucositis pathophysiology
GI mucosa is comprised of epithelial cells and has a rapid turnover rate
initiation of problem –> upregulation with generation of messengers –> signaling and amplification –> ulceration –> healing
may range from mild inflammation to bleeding ulcerations
can affect entire length of GI tract
Mucositis course parallels
the neutrophil nadir and begons on day 5-7 after chemo and improves as neutrophil count increases
Chemotherapy induced mucositis
continuous infusions > short IV infusions
many chemo drugs
Mucositis risk factors
pre-existing oral lesions
poor dental hygeine or ill-fitting dentures
combined modality treatment: patients receiving chemo and radiation
Mucositis prevention treatment
diet recommendations: avoid rough food, spices, salt and acidic fruit (lemons, grapefruit, oranges)
mainly eat soft or liquid foods, nonacidic fruits, soft cheeses, and eggs
avoid smoking and alcohol
Mucositis general mouth care strategies
pre-treatment dental screening, especially in pts receiving radiation therapy to the oral mucosa or those receiving high dose chemo with a bone marrow transplant
baking soda rinses: rinse 2-4 times daily
soft-bristled toothbrush to minimize gingival irritation
saliva substitute for radiation-induced xerostomia - radiation to mouth kills of salivary glands
Mucositis pain management - topical anesthetics
often provide adequate relief, but effect tends to be short-lived
various combos of lidocaine, diphenhydramine, and antacids (magic mouthwash) - pts should swish + spit every few hours PRN
Mucositis pain management - oral cryotherapy
“ice chips”
vasoconstriction may decrease chemo delivery to oropharyngeal mucosa
use ice chips 30 min prior to fluorouracil (5-FU) doses has been shown to decrease mucositis incidence and severity
Mucositis pain management: sucralfate
forms protective barrier
increases local production of prostaglandin E2, a mucosal protectant
swish + swallow
some pts find tast to be nauseating
Mucositis pain management: oral and parenteral opioid analgesics
often required in moderate to severe mucositis
many oral solutions contain high percent of alcohol, which may burn (don’t get these OTC)
opioids are best administered around the clock for pts with moderate to severe mucositis
use of patient-controlled analgesia pump is common
Neutropenia
white blood cells
megakaryocytes
red blood cells
White blood cells
normal range: 4.8-10.8 x 10^3/uL
decreased WBC = neutropenia (< 0.5 x 10^3/uL ), leukopenia, or granulocytopenia
risk of life-threatening infections
Megakaryocytes
decreased platelets = thrombocytopenia (< 100 x 10^3/uL)
normal range of 140-440 x 10^3/uL
risk of bleeding
Red blood cells
normal range of 4.6-6.2 x 10^12/L
decreased RBC = anemia
risks of hypoxia and fatigue
Neutropenia
bone marrow suppression is the most common dose-limiting toxicity of chemo
nadir (the absolute neutrophil count or ANC) is the lowest value the blood counts fall to during a cycle of chemo
occurs 10-14 days after chemo administration and counts usually recover by 3-4 weeks after chemo
exception: mitomycin C and nitrosoureas which nadirs 4-6 weeks after treatment
To administer chemo safely, the patient’s counts should be:
WBC > 3 x 10^3 uL OR
absolute neutrophil count (ANC) of > 1.5 x 10^3 uL AND platelet count >/= 100 x 10^3 uL
Important to look at the patient’s disease and goal of therapy
does the patient have a curable disease?
dictates what to do with the next cycle of chem: either dose reduce chemo or support with colony stimulating factors
Severe neutropenia
ANC < 0.5 x 10^3 uL
neutropenic patients are at an increased risk of developing serious infections
Febrile neutropenia
ANC < 0.5 x 10^3 uL and a single oral temp > 101 or >/= 100.4 for at least an hour
need to get treated with antibiotics
The usual s/s of infection
abscess, pus, infiltrates on chest x-ray, are absent with fever being the only reliable indicator
Colony stimulating factors
prophylactic use following chemo has demonstrated decreased: incidence of febrile neutropenia, length of hospitalization, confirmed infections, duration of antibiotics
ASCO and NCCN guidelines of CSFs - primary prophylaxis
primary prophylaxis: if pt is to receive chemo regimen that is expected to cause >/= 20% incididence of febrile neutrophenia
high risk pts: preexisting neutropenia due to disease, extensive prior chemo, previous irradiation to pelvis or other areas containing large amounts of bone marrow
ASCO guidelines of CSFs - secondary prophylaxis
pt experienced a neutropenic complication from a previous cycle of chemo and now you want to prevent that again
use CSF preventively with next cycle of chemo
Other uses for CSFs
used to support pts through dose dense chemo
can be used alone, after chemo, or in combo with plerixafor to mobilize peripheral blood progenitor cells
after stem cell transplant to reduce duration of severe neutropenia
Chemotherapy regimens associated with > 20% and 10-20% incidence of neutropenic fever
filgrastim
pegfilgrastim
sargramostim
Filgrastim
dose dependent elevation in neutrophil count, rapid drop in WBC and neutrophil count following discontinuation
Pegfilgrastim
much longer half-life
non-linear PK and clearance increases with increasing neutrophil count; when count increases, body starts to clear the drug
Biosimilars
Tbo-filgrastim is not considered a biosimilar
filgrastim-sndz was the 1st biosimilar approved, did not receive interchangeable status
Neulasta (pegfilgrastim)
self injector kit
give 24 hours after chemo so you don’t have to go back next day to get injection
Filgrastim dosing
start up to 3-4 days after completion of chemo and continue until post-nadir ANC recovery to normal or near normal levele
Pegfilgrastim dosing
start at least 24 hours after chemo and can be given up to 3-4 days after chemo
at least 14 days should elapse between dose and next cycle of chemo
same day therapy not recommended
OnPro body injector can be applied same day
Filgrastim and pegfilgrastim AEs
flu-like sx
bone and joint pain - attributed to rapid proliferation of bone marrow myeloid cells; can use acetaminophen/non-opioid analgesics to treat or loratidine (pain is due to histamine release)
DVT
splenic enlargement with long term use
Thrombocytopenia
platelet count < 100 x 10^3 uL
however, increased risk of bleeding occurs when platelet count is </= 20 x 10^3 uL and therefore may require transfusion; most do not transfuse until pt is symptomatic
ASCO guideline recommends threshold for platelet transfusion of
10 x 10^3 uL
platelet transfusion at higher levels may be indicated in patients with active bleeding
may also be administered prior to surgical procedures: 40-50 x 10^3 uL for major invasive procedures; > 20 x 10^3 uL for minor procedures
Causes of anemia
decreased RBC production: cancer therapy - radiation or chemo; tumor infiltration into bone marrow
decreased erythropoietin production: renal dysfunction
decreased body stores of vit B12, iron, or folic acid
blood loss
Significance of anemia in cancer
fatigue more troubling to cancer pts
low hemoglobin levels have been correlated with poor performance status which has been correlated with decreased survival
decreased QOL
Chemotherapy induced anemia
patients with Hgb <= 11 g/dL or >/= 2 g/dL drop from baseline should undergo a work-up:
CBC, review of peripheral smear, consider blood loss, nutrional losses, renal dysfunction, tranfuse pt per guidelines if immediate correction required, if not complete symptom assessment
Chemotherapy induced anemia if patient is symptomatic
transfuse as indicated
consider use of erythropoietic stimulating agents
perform iron studies: serum iron, total iron binding capacity, serum ferritin
Erythropoietin stimulating agents have a
black box warning
increase risk of death, MI, stroke, venous thromboembolism, and tumor progression or recurrence
ESAs are not recommended:
in pts receiving myelosuppressive chemo with curative intent
in pts with cancer not receiving chemo
in pts receiving non-myelosuppressive chemo
Consider using ESAs in
cancer and CKD
pts undergoing palliative chemo
pts w/o other identifiable causes
Risks and benefits of therapy of ESAs
one study showed decreased survival when taking ESAs to correct Hgb > 12 g/dL
one study showed no differences in survival when ESAs utilized
ESAs risks and benefits in cancer setting
risks: increased thrombotic events, possible decreased survival, time to tumor progression shortened
benefits: transfusion avoidance, gradual improvement in anemia related sx
Risks and benefits in RBC transfusions
risks: transfusion reactions, transfusion related circulatory overload, virus transmission, bacterial contamination, iron overload, increased thrombotic events, possible decreased survival
benefits: rapid increase of hemoglobin and hematocrit levels, rapid improvement in anemia related sx fatigue
Epoetin alfa
for chemotherapy-associated anemia
glycoprotein (lineage-specific) which stimulates RBC production
stimulates division and differentiation of committed erythroif progenitors in bone marrow
produced in kidney
endogenous production regulated by level of tissue oxygenation
Epoetin alfa dosing
dose should be adjusted to maintain the lowest Hgb level
if Hgb increases > 1 g/dL in a 2 week period, the dose should be decreased by 25% for epoetin alfa and 40% for darbepoetin
Darbepoetin
stimulates erythropoiesis by binding to epoetin receptor like eryhtropoietin
has addition of sialic acid –> prolonged half life
for anemia in pts with non-myeloid malignancies where anemia is caused by chemo
Iron in anemic cancer pts
all oncology pts who are prescribed ESA therapy should have baseline iron studies performed
serum ferritin, iron, iron saturation
if a pt is iron deficient, workup should be done, if no other causes for anemia is identified, oral iron supplementation is recommended
iron absorption will be decreased if food is eaten 2 hours before or 1 hour after ingestion
Patients with what should not receive iron therapy
an active infection
Iron types
low molecular weight iron dextran
iron sucrose
ferric gluconate
Myalgias/arthralgias toxicities
paclitaxel, docetaxel, anastrozole, letrozole, exemestane
tx: NSAIDS, pts may require opioids
Hemorrhagic cystitis toxicities
high dose cyclophosphamide
ifosfamide
from acrolein accumulation
tx: hydration, mesna - both used for prevention
Heart failure toxicities
anthracyclines, high dose cyclophosphamide, trastuzumab
tx: monitor cumulative dose, assess for risk factors, dexrazoxane
Peripheral neuropathy toxicities
taxanes, vinca alkaloids, platinums
tx: change infusion rates, adjunctive pain meds
Pulmonary toxicities
bleomycin
tx: corticosteroids
Mesna
should be used with standard ifosfamide doses of < 2.5 g/m^2/day to decrease risk of hemorrhagic cystitis
binds acrolein metabolite
Cardiac toxicity mechanism
formation of iron-dependent oxygen free radicals due to stable anthracycline-iron complexes, which cause catalysis of electron transfer
myocardium is more susceptible due to lower levels of enzymes capable of detoxifying oxygen free radicals compared with other tissues
Type I chemotherapy related cardiac dysfunction (anthracyclines) - acute
occurs immediately after a single dose or course of therapy with an anthracycline
uncommon and transient
may involve abnormal ECG findings, including QT-interval prolongation, ST-T wave changes, and arryhthmias; rarely CHF and/or pericarditis observed
not related to cumulative dose and is uncommon
Type I chemotherapy related cardiac dysfunction (anthracyclines) - chronic
congestive HF
is related to cumulative dose!
onset usually within a year of receiving anthracycline therapy; rapid onset and progression
common and life threatening
sx include: tachycardia, tachypnea, exercise intolerance, pulmonary and venous congestion, ventricular dilatation, poor perfusion, pleural effusion
once ejection fraction drops, its irreversible
Type I chemotherapy related cardiac dysfunction (anthracyclines) - late-onset
develops several years or even decades after therapy
manifests as ventricular dysfunction, CHF, conduction disturbances, and arrhythmias
occurs more often in childhood/adolescence cancer survivors who received anthracyclines
don’t reinitiate anthracycline
Cumulative cardiac toxicity
@450 mg/m^2, risk of toxicity really starts to increase
Type II chemotherapy related cardiac dysfunction
traztuzumab: does not appear to be dose related or occur in all pts
ranges widely in severity
not associated with cardiac damage (reversible)
mechanism involves EGFR pathway which normally blunts the effects of stress signaling pathways (stunning effect) that are required to maintain cardiac function, structure, and contractility
once EF improves, can restart therapy
if trastuzumab is given with anthracycline, incidence increases up to 27% cardiac toxicity
