Supportive Care: I Flashcards
complications of N/V
- most feared complication of chemo despite ___ nature
- can result in the inability to deliver intended dose of chemo
limited
- dehydration
- electrolyte
- abnormalities
- fatigue
- depression
before 5-HT3 anti-emetics, it was expected to vomit 5-12 times per day
Types of N/V
anticipatory
- ___ response conditioned by severity and duration of previous emetic reactions from prior cycles of chemo
- non-PCOL like hypnosis helpful
- can be provoked by sight, sound, or smell
learned
cancer patients have hightened senses
Types of N/V
Acute
- emetic response correlating with the administration of chemo
- within __ hours of receiving chem
Delayed
- Related to chemotherapy occurring > ___ hours following completion of chemotherapy
– Mechanism is not fully understood, but there is ↑
evidence that substance P binding to ___ receptor may play a role
24
24
neurokinin 1
Types of N/V
Breakthrough
- occurs even if on scheduled anti-emetics ___ to chemotherapy
Refractory
- persists despite ___ anti-emetics
- Failed other therapies
- prior
- appropriate
Patho of CINV
- Chemo is toxic to GI tract inducing damage to the epithelial cells
- Enterochromaffin cells lining the GI tract contain large stores of ___ that are released in massive quantities after exposure to chemo
- chemoreceptor trigger zone (CTZ)
stimulates the vomiting center - Located in the nucleus tractus solitarii in the ___ which stimulates the emetic response
- Input to the vomiting center from the higher cortical centers, pharynx, and GI
tract can induce emesis
- serotonin
- medulla
Neurotransmitters implicated in CINV (5)
- dopamine
- histamine
- acetylcholine
- serotonin
- substance P
highly emetogenic chemo (level 5)
single agent
- Carboplatin
- Carmustine
- Cisplatin
- Cyclophosphamide
- Dacarbazine
- Doxorubicin
- Epirubicin
- Fam-trastuzumab-deruxtecan
- Ifosfamide
- Mechlorethamine
- Melphalan
- Sacituzumab govitecan-hziy
- Streptozocin
Combo Chemo
when considering combo chemo, need to consider emetogenicity
- level 1 or 2 agents do not contribute to the emetogenicity of the regimen
- adding level 3 or 4 ___ the emetogenicity of the combo by 1 level per agent
- add the different levels together to decide on which antiemetics to use
increasing
Oral Anticancer Agents
Moderate to high emetic risk:
(≥ 30% risk) Prophylaxis required on days of oral anticancer agent administration
- Azacitidine
- Busulfan
- Ceritinib
- Cyclophosphamide
- Fedratinib
- Lomustine
- Midostaurin
- Mitotane
- Selinexor
- Temozolomide
Oral Anticancer Agents
Moderate to high emetic risk:
(≥ 30% risk) As needed dosing is initially appropriate on days of oral anticancer agent administration
- Adagrasib
- Elacestrant
- Avapritinib
- Binimetinib
- Bosutinib
- Cabozantinib
- Crizotinib
- Dabrafenib
- Enasidenib
- Encorafenib
- Estramustine
- Etoposide
- Imatinib
- Lenvatinib
- Niraparib
- Olaparib
- Procarbazine
- Rucaparib
risk factors for CINV
- women __ men
- younger __ older
- prior history of ___ and ___ sickness
- previous CINV tend to do worse
- anxiety/high pretreatment ___ of nausea
- chronic ethanol can be ___
- >
- >
- motion, morning
- anticipation
- protective
treatment guidelines
___ for acute N/V is based on the emetogenic potential of chemo
- ___ receptor antagonists may be substituted for each other
- oral efficacy = IV efficacy
prophylaxis
- 5HT3
highly emetogenic regimens
A) 4 drug
B) 3 drug
C) 3 drug
A) NK-1 antagonist, steroid, 5-HT3 antagonist, atypical anti-psychotic
B) atypical antipsychotic, 5HT-3 antagonist, steroid
C) NK-1 antagonist, steroid, 5-HT3 antagonist
These 3 agents can be added with any regimen and any emetogenicity if patients are experiencing these toxicities
+/- Lorazepam 0.5 mg to 2 mg PO or IV or sublingual either every 4 or 6 hours as needed
+/- H2 blocker or proton pump inhibitor
moderately emetogenic
A) 2 drug
B) 3 drug
C) 3 drugs
- steroid, 5-HT3
- anti-psychotic, steroid, 5-HT3
- NK-1, steroid, 5-HT3 antagonist
low emetogenic regimens
only 1 needed
- steroid ( ___ )
- metoclopramide
- prochlorperazine
- 5-HT3 (3)
- dexamethasone
- dolasetron, granisetron, ondansetron
Breakthrough Nausea and Vomiting
give an additional agent from a different drug class as needed
- haloperidol or metoclopramide
- prochlorperazine or promethazine
- olanzapine
- lorazepam
- dronabinol or nabilone
- dolasetron, granisetron, or ondansetron
- dexamethazone
- scopolamine
Depending on the severity of the N/V, you can schedule these agents
Delayed Nausea and Vomiting
typically involves use of one of the following (3)
- dexamethasone
- NK-1 antagonist
- olanzapine
Anticipatory N/V
___ - Use optimal antiemetic therapy during
every cycle of treatment
___ - 0.5 to 1 mg orally beginning the night before treatment and then again 1 to 2 hours prior to beginning of
chemotherapy
- prevention
- lorazepam
other prevention guidelines
Oral chemotherapy - High to moderate emetogenic risk
- Start ___ chemotherapy and continue daily
- ___ antagonists
Low to minimal emetogenic risk
- Start ___ chemotherapy and maybe given daily or prn
– ___
– ___
– ___ antagonists
- before
- 5-HT3
- before
- Metoclopramide
- Prochlorperazine
- 5-HT3
Other Prevention Guidelines
Radiation Induced Emesis
- Start pretreatment for each day of radiation
therapy
- ___ PO +/- dexamethasone
- ___ PO +/- dexamethasone
Granisetron
Ondansetron
Radiopharmaceuticals
- Nausea is associated with the ___ infusion accompanying treatment
- Antiemetics should be given ___ minutes prior to start of infusion
Recommendations for antiemetics include:
- ___ or ___ antagonists
- NOT ___ due to down regulation of somatostatin receptors
- amino acid
- 30
- 5-HT3, NK-1
- steroids
Common Toxicities Across Classes
Serotonin (5-HT3) antagonists
- Ondansetron
- Granisetron
- Dolasetron
- Palonosetron single agent or combination products (+/- netupitant
or fosnetupitant)
- Headache
- asymptomatic and transient EKG changes (max doses)
- constipation
- increased transaminases
Common Toxicities Across Classes
Corticosteroids
- Dexamethasone
(Short term use):
- Anxiety
- euphoria
- insomnia
- hyperglycemia
- ↑’d appetite
Common Toxicities Across Classes
Substance P antagonists
- Aprepitant
- Aprepitant injectable emulsion
- Fosaprepitant
- Rolapitant
- Netupitant
- Fosnetupitan
- Hiccups
- worry about drug
interactions
Common Toxicities Across Classes
Dopamine antagonists
- Chlorpromazine
- Haloperidol
- Metoclopramide
- Extrapyramidal side effects
- diarrhea
- sedation
Common Toxicities Across Classes
Atypical antipsychotic
- Olanzapine
- dystonic reactions
- sedation
Common Toxicities Across Classes
Phenothiazines
- Prochlorperazine
- Promethazine
- Sedation
- akathesia
- dystonia
- IV promethazine = tissue damage
Common Toxicities Across Classes
Cannibanoids
- Dronabinol
- Drowsiness
- dizziness
- euphoria
- mood changes
- hallucinations
- ↑’d appetite
Common Toxicities Across Classes
Benzodiazepines
- Lorazepam
- sedation
- hypotension
- urinary
- incontinence
- hallucinations
Common Toxicities Across Classes
Anticholinergic
- Scopolamine Patch
- Anti-cholinergic side effects
Important Principles for Prevention and Management
- Review medical history, diagnosis, and
concurrent medications
– Consider any contributing causes to
nausea/vomiting, and treat appropriately
– ___ is a risk with phenothiazines and
metoclopramide - Evaluate the emetogenic potential and
pattern of the chemotherapeutic regimen to be given
EPS
Important Principles for Prevention and Management
- Emetogenicity is ___
- Emetogenic potential may be different on different days of treatment (stronger day 1 than 2 and 3)
- acute/delayed N/V
- most guidelines are tailored to chemo on day 1
additive
Important Principles for Prevention and Management
T or F: Anti-emetics are most effective when given as
prophylaxis
T
- Begin therapy at least 5 to 30 minutes prior to
chemo
- Administer around-the-clock until chemo is complete and provide PRN agents for breakthrough N/V
- Always provide patients with additional PRN anti-emetics to take home
Mucositis
GI mucosa is comprised of epithelial cells and has a rapid turnover rate
- Initiation -> Up-regulation with generation of messengers -> Signaling and amplification -> Ulceration -> Healing
- range from mild inflammation to bleeding ulcerations
- It can affect the entire length of the GI tract from top to bottom
- Course parallels the neutrophil nadir and begins on day 5 to 7 after chemotherapy and improves as the neutrophil count ___
increases
chemo induced mucositis
Continuous infusions ___ short IV infusions
>
risk factors to mucositis
- Pre-existing oral lesions
- Poor dental hygiene or ill-fitting dentures
- Combined modality treatment ( ___ + ___ )
- chem + radiation
Prevention and Treatment
Diet recommendations:
– Avoid rough food, spices, salt and acidic fruit
– Mainly eat soft or liquid foods nonacidic fruits, soft cheeses,
and eggs
– Avoid ___ and alcohol
Pre-treatment dental screening, especially in patients receiving ___ therapy to the oral mucosa or those receiving high-dose
chemo with a ___ transplant
– Baking soda rinses, soft-bristled toothbrush to minimize gingival
irritation, saliva substitute for radiation-induced xerostomia
- smoking
- radiation
- bone marrow
Pain Management - mucositis
Topical anesthetics
– Often provide adequate relief, but the effect tends to be short-lived
– Various combinations of lidocaine,
diphenhydramine, and antacids have been used with success ( ___ ___ )
- Patients should be instructed to swish and spit or swallow depending on the location of the mucositis) every few hours as needed
Ice Chips - vaso ___ decreased chemo delivery to mouth
- 30 min prior to ___ doses decreases incidence/severity
Sucralfate
- nauseating
magic mouthwash
vasoconstriction
5-FU
Pain Management - mucositis
Oral and parenteral opioid analgesics
- Often required in moderate to severe mucositis
- Many oral solutions contain a high percentage of alcohol, which may burn (dont get OTC)
- Opioids are best administered ___ for patients with moderate to severe mucositis
- Use of ___ is common
- around the clock
- PCA
neutropenia
White blood cells (WBC):
- Normal range of 4.8-10.8 x10 3 /μL
- Decreased WBC = Neutropenia (< 0.5 x 103 /μL), leukopenia, or granulocytopenia
- Risk of life-threatening ___
Megakaryocytes (platelets)
- Normal range of 140 - 440 x 10 3 /μL
- ___ platelets = Thrombocytopenia (< 100 x 103 /μL)
- Risk of ___
Red blood cells (RBC)
- Normal range of 4.6 to 6.2 x1012 /L
- Decreased RBC = ___
- Risks of hypoxia and __
- infection
- decreased
- bleeding
- anemia
- fatigue
Neutropenia
___ suppression is the most common dose-limiting toxicity of chemo
The ___ (usually described by the absolute neutrophil count or ANC) is the lowest value the blood counts fall to during a cycle of chemo
- Generally, occurs ___to ___ days after chemo administration and counts usually recover by 3 to 4
weeks after
- Some exceptions include mitomycin C and nitrosoureas which nadirs 4 - 6 weeks after treatment
- bone marrow
- nadir
- 10, 14
Neutropenia
ANC = WBC x % granulocytes (Segs + Bands)
- To administer chemotherapy safely the patient’s counts should be as assessed prior to administration. These are typical guidelines:
– WBC > __ x103 /μL OR
– Absolute neutrophil count (ANC) of > ___ x103 /μL AND platelet count > ___ x103 /μL
- 3
- 1.5, 100
neutropenia
Severe neutropenia is defined as ANC < ___ x 103 /μL
* Neutropenic patients are at an ↑’d risk of developing serious infections
* ___ neutropenia (FN) is defined as:
– ANC < 0.5 x 103 /μL and a single oral temperature > 101°F (> 38.3°C) or > 100.4°F (> 38.0°C) for at least an hour
- 0.5
- febrile
neutropenia
Other factors affecting myelosuppression:
- previous chemotherapy
- previous radiation therapy
- direct bone marrow involvement
neutropenia
T or F: The usual s/s of infection (abscess, pus, infiltrates on chest x-ray) are absent with fever being the only reliable indicator
T
WBC low = no pus
Colony Stimulating Factors (CSFs)
Prophylactic use following chemo has demonstrated decreased:
- Incidence of ___ neutropenia
- Length of hospitalization
- Confirmed ___
- Duration of ___
- febrile
- infections
- antibiotics
CSF guidelines (ASCO NCCN)
Primary prophylaxis
If the patient is to receive a chemo regimen that is expected to cause > 20% incidence of ___ neutropenia
High risk patients defined as:
- Preexisting neutropenia due to disease
- Extensive prior chemo
- Previous irradiation to the pelvis or other areas containing large amounts of ___
- febrile
- bone marrow
CSF guidelines (ASCO)
Secondary prophylaxis
- The patient experienced a neutropenic complication from a previous cycle of chemo and now you want to prevent
that again
– Use a CSF ___ with next cycle of
chemo
preventively
Other uses for CSF’s:
- Used to support patients through dose ___ chemo
- Can be used alone, after chemo, or in combination with ___ to mobilize peripheral blood progenitor cells
- After a __ transplant to reduce the duration of severe neutropenia
- Guidelines for pediatric use are available and should be followed
- dense
- plerixafor
- stem cell
CSF agents (3)
- filgrastim
- pegfilgrastim
- sargramostim
CSF - filgrastim
- Regulates the production, maturation, and function of neutrophil cell line
- Dose dependent elevation in neutrophil count, rapid drop in WBC and neutrophil count following ___ (approximately 50% decrease within 24 hours)
discontinuation
CSF - pegfilgrastim
- Differs from filgrastim due to a 20-kD pegylated molecule that is attached to
the N-terminus of filgrastim - Stimulates production & maturation of neutrophil precursors like filgrastim
- ___ pharmacokinetics & clearance ___ with increasing
neutrophil count
- Non-linear
- increases
CSF - Sargramostim
- Effects on phagocytic accessory cells which mediates its action on the neutrophil lineage
- Drop in WBC & neutrophil count following ___ (approximately 50% decrease within 24 hours)
- discontinuation
CSF - Biosimilars: Similar or Not?
- Tbo-Filgrastim (Granix)
- Filgrastim-sndz (Zarxio)
- Filgrastim-aafi (Nivestym)
- Filgrastim-ayow (Releuko)
Tbo-filgrastim is not considered a biosimilar and received an original biologic license through the FDA
- Filgrastim-sndz was the first biosimilar approved in the US in March 2015
- Did NOT receive interchangeable status
Patient should remain on whichever agent it is started on and not switch between manufactured products
Dosing and Adverse Effects
Filgrastim: 5 mcg/kg/day
– Start up to 3 - 4 days ___ completion of chemotherapy and continue until post-nadir ANC recovery to ___ ish levels
- after
- normal
Dosing and Adverse Effects
Pegfilgrastim: 6 mg SQ x 1 dose
- Start at least 24 hours ___ chemo and can be given up to 3 – 4 days after chemo
- At least __ days should elapse between dose and the next
cycle of chemo
- Same day therapy is generally not recommended
- OnPro® body injector can be applied same day
after
14
CSF Adverse Effects
- Flu-like symptoms
- bone and joint pain
- DVT
CSF Adverse Effects
Bone or musculoskeletal pain occurs in 20-30% of patients receiving CSF’s
- Attributed to rapid proliferation of the bone marrow myeloid cells
- Can use acetaminophen/non-opioid analgesics
- Data with use of ___ . Why? Thought is that pain is due to histamine release.
Rare Adverse Effects
- ___ enlargement with long term CSF use
- loratidine
- splenic
Thrombocytopenia
Usually defined as a platelet count
< ___ x 10 3 /μL, however increased risk of bleeding occurs when platelet count is < 20 x 10 3 /μL and therefore may require transfusion
- Most institutions do not transfuse until patient becomes ___
- ASCO guideline recommends a threshold for platelet transfusion of ___ x 10 3 /μL
- 100
- symptomatic
- 10
General Causes of Anemia
Decreased red blood cell production
- Cancer therapy: Radiation or chemo
- Tumor infiltration into the ___
Decreased erythropoietin production
- ___ dysfunction
- Decreased body stores of vitamin B12, iron, or folic acid
- Blood loss
- bone marrow
- renal
Significance of Anemia in Cancer
Fatigue has been reported in several
surveys as more troubling to cancer patients than nausea, vomiting, or pain
- Low ___ levels have been correlated with poor performance status which has been correlated with decreased survival and quality of life
hemoglobin
Chemotherapy Induced Anemia
Patients with a Hgb ≤ __ g/dL or ≥ __ g/dL drop from baseline should undergo a work-up:
11, 2
Chemotherapy Induced Anemia
If patient is symptomatic:
- ___ as indicated
- Consider use of ___
- Perform ___ studies:
- transfuse
- ESA
- iron
patients need to be counseled on the risks and benefits of therapy
ESA warnings
WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE
boxed warnings
Considerations for Use of ESA’s
ESAs are NOT recommended:
– In patients receiving myelosuppressive chemotherapy
with ___ intent
– In patients with cancer NOT receiving chemo
– In patients receiving non- ___ chemo
- curative
- myelosuppressive
Considerations for Use of ESA’s
Consider using:
– Cancer and ___
– Patient’s undergoing ___ chemotherapy
– Patients without other identifiable causes
- CKD
- palliative
Risks and Benefits of Therapy
Survival studies:
- 3 meta-analyses demonstrated ___ survival when taking ESAs to correct Hgb > 12 g/dL
- 2 meta-analysis did not show differences in survival
when ESAs utilized
- Additional ongoing trials are underway to guide optimal use
- decreased
Risk and Benefits of Therapy
Risks
1. Increased ___ events
2. Possible ___ survival
3. Time to tumor progression ___
Benefits
1. ___ avoidance
2. Gradual improvement in
___ related symptoms
- thrombotic
- decreased
- shortened
- transfusion
- anemia
Risk and Benefits of Therapy
Risks
1. Transfusion ___
2. Transfusion related circulatory overload
3. Virus transmission (hepatitis, HIV,
etc.)
4. Bacterial contamination
5. Iron overload
6. Increased ___ events
7. Possible decreased survival
Benefits
1. Rapid increase of ___
and hematocrit levels
2. Rapid improvement in anemia
related symptoms like ___
- reactions
- thrombotic
- hemoglobin
- fatigue
Epoetin alfa (Erythropoietin, Epoetin)
Pharmacology
- Glycoprotein which stimulates ___ production
- Stimulates ___ and ___ of committed
erythroid progenitors in the bone marrow
- Produced in the ___
- Endogenous production regulated by level of tissue oxygenation
- RBC
- division, differentiation
- kidney
Epoetin alfa (Erythropoietin, Epoetin)
For chemotherapy-associated anemia
- Dose should be adjusted to maintain the ___ Hgb level
- If the Hgb increases > __ g/dL in a 2-week period, the dose should be decreased by __ % for epoetin alfa and __ % for darbepoetin
- lowest
- 1
- 25, 40
Darbepoetin (Aranesp)
Stimulates erythropoiesis by binding to the ___ receptor like erythropoietin
- Biochemically distinct from epoetin alfa by the addition of a sialic acid
- half life 2 - 3 x ___ than epoetin
Indications
- Anemia in patients with non- ___
malignancies where anemia is caused by chemo
Dosing
- Titrate to response same as with epoetin alfa
- epoetin
- longer
- myeloid
Iron in Anemic Cancer Patients
T or F: All oncology patients who are prescribed ESA therapy should have baseline iron studies performed
T
Iron in Anemic Cancer Patients
Serum ferritin, iron, iron saturation
- If a patient is iron deficient, a workup should be done
- If no other causes for anemia is identified, oral iron supplementation is ___
- Iron absorption will be ___ (by as much as half) if food is eaten 2 hours before or 1 hour after ingestion
- recommended
- decreased
Iron Dosing
- Low Molecular Weight Iron Dextran (Dexferrum) - IV ___
- Iron Sucrose (Venofer) - IV ___ , ___
- Ferric Gluconate (Ferrlecit) - IV ___ , ___
Patients with an active ___ should not receive iron therapy
- infusion
- infusion, injection
- infusion, injection
- infection
Classic Chemotherapy Toxicities
Toxicity: Myalgias/Arthralgias
Chemo (5)
Treatment (2)
- Paclitaxel, Docetaxel
Anastrozole, Letrozole,
Exemestane - NSAIDs, opioids
Classic Chemotherapy Toxicities
Toxicity: Hemorrhagic cystitis
Chemo (2)
Treatment (2)
- High dose cyclophosphamide,
Ifosfamide - Hydration (prevention), Mesna (prevention)
Classic Chemotherapy Toxicities
Toxicity: Heart Failure
Chemo (3)
Treatment (3)
- Anthracyclines, High dose cyclophosphamide, Trastuzumab (other HER2 targeted therapies)
- Monitor cumulative dose, assess for risk factors, Dexrazoxane (chemoprotectant)
Classic Chemotherapy Toxicities
Toxicity: Peripheral Neuropathy
Chemo (3)
Treatment (2)
- Taxanes, Vinca Alkaloids,
Platinums - Change infusion rates (i.e., Paclitaxel), Adjunctive pain medications (ex. Gabapentin, amitriptyline)
Classic Chemotherapy Toxicities
Toxicity: Pulmonary
Chemo: (1)
Treatments (1)
- bleomycin
- Corticosteroids (no good treatment once
it happens)
Mesna
Mesna should be used with standard
ifosfamide ( ___ ) doses of < 2.5 g/m2 /day to decrease risk of hemorrhagic cystitis
- toxic metabolite: ___
- cyclophosphamide
- acrolein
Cardiac Toxicity
Mechanism
- Formation of iron-dependent oxygen free ___ due to stable anthracycline-iron complexes, which cause catalysis of electron transfer
- Myocardium is more susceptible due to lower levels of ___ capable of detoxifying oxygen free radicals compared with other tissues
- radicals
- enzymes
Type I Chemotherapy Related: Cardiac Dysfunction
Acute
- Occurs immediately after a single dose or course of therapy with an ___
- Uncommon and transient
- May involve abnormal ECG findings, including QT-interval prolongation, ST-T wave changes,
and arrhythmias
- Rarely, CHF and/or pericarditis are observed
- Not related to cumulative dose and is uncommon
anthracycline
Type I Chemotherapy Related: Cardiac Dysfunction
Chronic
- Onset usually within a ___ of receiving ___ therapy
- Rapid onset and progression
- Common and life threatening
- Related to ___ dose patient received
- Symptoms include tachycardia, tachypnea, exercise intolerance, pulmonary and venous congestion, ventricular dilatation, poor perfusion, and pleural effusion
- year
- anthracycline
- cumulative
Type I Chemotherapy Related Cardiac Dysfunction
Late-onset
- Develops several years or even ___ after therapy
- Manifests as ventricular dysfunction, CHF, conduction disturbances, and arrhythmias
- Occurs more often in childhood / adolescence cancer survivors who received ___
- decades
- anthracyclines
Type II Chemotherapy Related Cardiac Dysfunction
Trastuzumab
- Does not appear to be dose related or occur in all patients
- Ranges widely in severity
- Has not been associated with cardiac ___
- Mechanism involves ___ pathway which normally blunts the effects of stress signaling pathways (a stunning effect) that are required to maintain cardiac function, structure, and contractility
- damage
- EGFR
Type II Chemotherapy Related Cardiac Dysfunction
Trastuzumab
- Appears to be largely ___ and short lived
- Incidence is ~ 3% in non-anthracycline treated patients and increases to 5% in those who have received previous anthracyclines
- If trastuzumab is given ___ with anthracycline, the incidence can increase up to ___ % cardiac toxicity (NYHA class III/IV)
- reversible
- concurrently
- 27%
