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

Supportive Care: I Flashcards by Reagan Smith

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

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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

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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

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Types of N/V

Breakthrough
- occurs even if on scheduled anti-emetics ___ to chemotherapy

Refractory
- persists despite ___ anti-emetics
- Failed other therapies

prior
appropriate

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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

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Neurotransmitters implicated in CINV (5)

dopamine
histamine
acetylcholine
serotonin
substance P

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highly emetogenic chemo (level 5)

single agent

Carboplatin
Carmustine
Cisplatin
Cyclophosphamide
Dacarbazine
Doxorubicin
Epirubicin
Fam-trastuzumab-deruxtecan
Ifosfamide
Mechlorethamine
Melphalan
Sacituzumab govitecan-hziy
Streptozocin

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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

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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

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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

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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

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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

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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

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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

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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

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low emetogenic regimens

only 1 needed
- steroid ( ___ )
- metoclopramide
- prochlorperazine
- 5-HT3 (3)

dexamethasone
dolasetron, granisetron, ondansetron

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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

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Delayed Nausea and Vomiting

typically involves use of one of the following (3)

dexamethasone
NK-1 antagonist
olanzapine

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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

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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

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Other Prevention Guidelines

Radiation Induced Emesis
- Start pretreatment for each day of radiation
therapy
- ___ PO +/- dexamethasone
- ___ PO +/- dexamethasone

Granisetron
Ondansetron

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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

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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

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Common Toxicities Across Classes

Corticosteroids
- Dexamethasone

(Short term use):
- Anxiety
- euphoria
- insomnia
- hyperglycemia
- ↑’d appetite

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# 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? 1. Tbo-Filgrastim (Granix) 2. Filgrastim-sndz (Zarxio) 3. Filgrastim-aafi (Nivestym) 4. 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

# 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%

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Supportive Care: I Flashcards

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