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IPFC 6 > Myelosuppresion + GI toxicity > Flashcards

Myelosuppresion + GI toxicity Flashcards

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1
Q

What conditions do myelosuppresion entail (3)

A
  • Low neutrophils -> neutropenia
  • Low RBCs -> Anemia
  • Low platelets -> Thrombocytopenia
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2
Q

Treatments that cause myelosuppression

A
  • Radiation
  • Cytotoxic chemotherapy
  • Monoclonal antibodies
  • Targeted agents
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3
Q

Treatments that can cause myelosuppresion

A
  • Radiation
  • Cytotoxic chemo
  • Monoclonal antibodies
  • targeted agents
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4
Q
A
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5
Q

Why is cancer therapy myelosuppressive in these classes
Cytotoxic chemotherapy
Targeted agents
Anti-CD20

A

Cytotoxic chemotherapy
- directly destroys dividng stem cells

Targeted agents
- Interfere with cellular signaling that is part of hematopoiesis

Anti-CD20
- cause deletion of B-cells

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6
Q

Which myelosuppression was the most common DOSE-limiting toxicity associated with chemotherapy

A

Neutropenia

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7
Q

What are risk factors for neutropenia and its complications

A

Type of chemo
- Cytotoxic chemo is most common. Also with some targeted agents (CDK4/6, BTK inhibitors)
- Most BREAST cancer regimens, many HEME cancer regimens and CHEMORADIOTHERAPY for LUNG cancer have high risk of neutropenia

Initial cycle (if it doesn’t happen in the first, wont happen)
Older age
Female sex
Baseline status: WBC count, performance status
Dysfunction: hepatic, renal

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8
Q

What grade of neutropenia would you intervene in and lower dose

A

Grade 3 or 4

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9
Q

Define febrile neutropenia? Cause?

A

Defined as a fever for at least an hour and in the setting of neutropenia
- infectious cause

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10
Q

When to treat febrile neutropenia
What to use normally
for low risk
MRSA risk

A

Treat when they have fever + under the LLN of neutrophils

What to use normally
- Treat empirically with broad spectrum antibiotics
- Piptaz, carbapenem, ceftazidime

for low risk
- manage as outpatient with Ciprofloxacin + Cephalosporin

MRSA risk
- add vanco

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11
Q

What drug class is given as prophylaxis? when is it given?

A

G-CSF
(Granulocyte colony stimulating factors)
(filgrastim, pegfilgrastim)
- boosts WBC count
- only give when its curative intent

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12
Q

What risk assessment do you do when giving prophylaxis for FN

A

Disease type
Chemo regimen
Patient risk factors
Neutropenia with previous cycle
Treatment intent (has to be curative)

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13
Q

Differentiate between Filgrastim and pegfilgrastim
Dose
Start
ADRs (3)

A

Filgrastim
- DAILY SC 24-72 hrs after for 7-10 days

pegfilgrastim
- ONCE SC 24 hours after chemo

ADRs
- bone pain (large bones like skull, femer, spine)
- Injection site reactions
- Anaphylaxis

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14
Q

What are the benefits of GCSF prophylaxis

A

They cause the NADIR (10-14 days after dose where neutrophils are the lowest) to occur EARLIER and LESS SEVERELY
- Result is an EARLIER and BETTER recovery from the neutropenic state

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15
Q

What patient risk factors are intermediate that you would consider GCSF

A
  • prior chemo or radiation
  • Persistent neutropenia
  • Bone marrow involvement by tumour
  • Recent surgery
  • Liver dysfunction
  • Renal dysfunction
  • Age 65+ receiving full chemo dose intensity
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16
Q

What are other preventative measure of febrile neutropenia

A
  • Frequent hand washing. Especially around Nadir period
  • Hand sanitize frequent
  • Avoid crowded conditions, people with contagious conditions (colds, etc.)

If patient develops fever of >38C lasting >1 hour OR >38.3C at any time -> contact hospital IMMEDIATELY

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17
Q

How does cancer treatment cause anemia? (5)

A
  • Chemo/radiation
  • Anemia of cancer (chronic disease) (impaired erythropoietin production/response, impaired iron re-utilization)
  • Blood loss
  • Nutritional deficiency
  • Hemolysis
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18
Q

What are risk factors for cancer-related anemia

A
  • Tumour type
  • Stage and duration of disease
  • regimen and intensity of tumour therapy (platinum agents known for anemia)
  • Presence of infection
  • Surgical intervention
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19
Q

What are symptoms of anemia in cancer patients?
Which one is the greatest?

A

FATIGUE, dizziness, depression
Anorexia, Nausea
Low skin temp, pallor skin
Increased tachy, palipiation

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20
Q

T/F Anemia Fatigue is relieved by sleep or rest in cancer patients

A

False

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21
Q

What hgb levels does fatigue increase significantly in

A

<120 hgb

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22
Q

When are RBC transfusions indicated in anemia (2)

A
  1. Rapid correction of Hb
  2. Increase in blood volume
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23
Q

What are drawbacks of using RBC transfusion

A
  1. The effect of RBC transfusion are short lived
  2. It does not address the underlying process of anemia
  3. There are risks associated with RBC transfusion
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24
Q

What are the ADRs of RBC transfusion
Serious (4)
Mild (2)

A

Serious ADRs
- Transmission of infection (viral, HIV, hepatitis, bacterial)
- Acute and delayed hemolytic reactions
- Immunosuppression
- Transfuion-related acute lung injury

Mild
- Fever
- urticaria

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25
What erythropoetic agents are used in anemia
Eprex Longer hald life - Aranesp - Darbopoetin
26
What is the evidence of using erythropoietic agents (2)
- Improves QoL - decreases # of transfusions used
27
What ADR is associated with using erythropoietic agents? In which groups of patients is it related to?
Risk of thrombosis - In pts with Hgb over 120g/L - In pts with rapid rise in Hgb over 10g/L in any 2 week period
28
What reasons do patients need to have in order to get funding for Erythropoietic agents (4)
- Religious beliefs - Previous severe reaction to transfusion - Myeloid cancers (due to frequency of transfuisons) - Live in remote location
29
When are iron infusions used in cancer patients? what lab values do they have to have (3) Which one do we use?
(venofer) Iron sucrose 100mg weekly for 3 weeks Patient - Normal ferritin - Low TSAT - Low serum iron
30
Which agents cause thrombocytopenia
- Cytotoxic chemo - BCR-ABL TKIs - VEGF/VEGFR inhibitors - PARP inhibitors - BCL-2 inhibitors - CDK 4/6 inhibitors - BTK inhibitors
31
What treatment do you provide for the following grading of thrombocytopenia Grade 1 Grade 2 Grade 3 Grade 4
Grade 1 - no changes Grade 2 - Delay/hold causative agent Grade 3 (risk of bleeding increases) - with active bleeding = platelet transfusion - consider reducing dose Grade 4 (risk of life-threatening bleed) - platelet transfusion - d/c agent (likely due to disease (acute leukemia) than the drug agent
32
What are patient-specific factors for CINV? (5)
- Younger Age - Female - Alcohol use (non-drinkers more prone) - History of motion sickness or pregnancy related n/v - Anxiety
33
What are disease specific risk factors for CINV (5)
- Tumour location: GI, brain, liver - Fluid/electrolyte imbalances - Constipation - Ileus - Kidney dysfunction
34
Which drugs are 5HT3 serotonin antagonists (3)
First gen - Ondansetron - Granisetron 2nd gen agent - Palonosetron
35
What does evidence say of use in Ondansetron (1st gen) vs Palonosetron (2nd gen) in MEC and HEC
Palonosetron is better
36
What is the indication for 5HT3 antagonists
For ACUTE events for MEC and HEC
37
What ADRs are associated with 5HT3 antagonists (3)
Headache Constipation Transient inc in LFTs
38
What drugs are substance P/NK1 receptor antagonist (2)
Aprepitant Netupitant/Palonosetron
39
What is the indication of NK1 receptor antagonist (2)
for ACUTE + prevention of delayed events (combo = Akynzeo) For HEC or refractory MEC mod-severe CINV
40
What does evidence say of palonestron vs Akynzeo (combo of 5HT3 + NK1)
Combo is more effective in acute and delayed
41
What are ADRs associated with NK1 receptor antagonist (2)
- Fatigue/asthenia (lack of energy) - hiccups
42
Which corticosteroids are used in CINV? What is it synergistic with?
Dexamethasone - synergistic with 5HT3 (ondansetron)
43
Indication for corticosteroid in CINV
for prevention of DELAYED CINV for all MEC and HEC (multi-day with HEC)
44
What are the ADRs with corticosteroids
- Hyperglycemia - Psychosis - insomnia - dyspepsia - hiccups (caution in diabetics)
45
What are the D2 antagonists used in CINV (5)
- Prochlorperazine - Metoclopramide - Domperidone - Haloperidol - Olanzapine
46
What is the indication for D2 antagonists
For BREAKTHROUGH nausea in conjunction with other agents Can be for prevention in HEC/MEC
47
What are ADRs of D2 antagonist (3)
- Sedation - Hypotension - Extrapyramidal symptoms (affect motor activity)
48
What are benzodiazepines indicated for in CINV? Which one is used
Lorazepam Used for anticipatory nausea - someones for breakthrough in combo
49
What are cannabinoids indicated for in CINV? Which one is used?
Nabilone For BREAKTHROUGH nausea (+ help appetite) - Used as last resort
50
What interaction with dexamethasone do we have to be careful with in dosing
If on Aprepitant (3A4 inhibitor): max dose of Dex 12mg (3A4 substrate)
51
Sumarize CNIV drugs for HEC Acute Day 1 (4) Delayed (3)
Acute Day 1 (4) 1. NEPA (combo) 2. 5-HT3 inhibitor 3. Dexamethasone 4. Olanzapine Delayed (3) 1. Aprepitant (if applicable) 2. Dexamathesone (days 2-4, if applicable) 3. Olanzapine (days 2-4)
52
Sumarize CNIV drugs for MEC (2) Acute (2) Delayed (2) Breakthrough
Acute Day 1: 1. 5HT3 receptor antagonist (ondansetron) 2. Dexamethasone (give additional 3 days) Delayed 1. if inadequate control can choose NK1 (aprepitant) 2. olanzapine for subsequent days (5days) 3. Can switch to NEPA on day 1 Breakthrough - D2 antagonist (prochlorperazine)
53
Sumarize CNIV drugs for LEC (1)
Dexamethasone day of chemo
54
Sumarize CNIV drugs for Minimal EC (1)
No antiemetics recommended
55
What are some non-pharmacologic recommendations for CINV
- Smaller, more frequent meals - 8-12 glasses per day - Avoid hot, spicy and fatty foods - If 6+ episodes in 24 hours contact clinic
56
What are symptoms of mucositis (3) Symptoms if it extends down the whole GI tract (2)
The lining of the mouth and throat has: - Erythema - Swelling - Ulceration Can extend down the whole GI tract - can lead to heartburn/diarrhea symptoms
57
When does mucositis present? How long does it last?
Onset: 5-8 days after chemo or 2 weeks after start of radiation Duration: 7-14 days
58
What are some of the causative agents of mucositis (4)
- Hematopoietic stem cell transplant (HSCT) patients (many need full TPN as a result) - Head/neck rads + 5-FU - Cytotoxic chemo ○ Anthracyclines, Antimetabolites, - Topoisomerase inhibitors, Taxanes ○ Vinca alkaloids ○ Alkylating agents - Targeted agents (mTOR inhibitors)
59
T/F after mucositis is healed the mucosa appears normal
True - ONLY appears normal, but significantly altered - inc vulnerability to future episodes
60
What are risk factors of mucositis (6)
- Chemo: type, dose, combo with radiation - Location of radiation (head/neck is high risk) - Age (younger) - Female > male - Poor oral hygiene - Xerostomia
61
What drug is used for prevention of radiation induced mucositis
Benzydamine 0.15% mouthwash rinse (Q2-3h up to 8x/day)
62
What is used for prevention in 5-FU based regigmens Which treatment do you have to be cautious with when using?
Oral cryotherapy (ice chips in mouth) HOWEVER, 5-FU is commonly part of FOLFOX (includes oxaliplatin) - CAN'T use ice chips with oxaliplatin - cold-induced neuropathy
63
What is used for prevention in HSCT (hematopoietic stem cell transplant) patients
Palifermin
64
What other therapies are validated by MASCC guidelines for mucositis
Laser therapy Oral care protocols
65
What is NOT recommended in MASCC guidelines for mucositis
- Chlorohexidine - Antimicrobial lozenges - Sucralfate - Acyclovir
66
What does the oral care protocol entail for mucositis (6)
- Soft toothbrush 2-3x/day - Regular flossing (DON'T START if you don't floss) - Alcohol-free mouthwashes - Mouth rinse (baking soda, saline, club soda) - Inspect oral cavity daily - Dentures properly fit
67
What is the efficacy of the benzydamine mouth wash What kind of properties does this mouth wasah have (4)
Decrease severity AND frequency of radiation induced mucositis Anti-inflammatory Analgesic Anesthetic Antimicrobial
68
What is the efficacy of cryotherapy
Leads to vasoconstriction - Reduces amount of 5-FU reaching mucosa 50% reduction in frequency of mucositis
69
What is the efficacy of Palifermin
Mitogenic effect on mucosal epithelium Reduced incidence AND DURATION of severe mucositis
70
What are ADRs of palifermin? (5) Most common?
- Rash (most common) - Edema - Tingling.itching - thickness/discolouration of tongue/mouth - Arthralgias
71
What is used for prevention of mTOR induced mucositis
Dexamethasone
72
What is the current standard for symptomatic relief of mucositis
1/3 lidocaine 1/3 nystatin 1/3 distilled water sugar-free kool-aid powder Swish and swallow 5-10 mL QID
73
What are causative agents of diarrhea?
Cytotoxic chemo - Antimetabolites (EXPECIALLY 5FU/Capecitabine) - Irinotecan!! THE WORST - Taxanes Targeted agents - CDK 4/6 inhibitors - EGFR inhibitors COMMON - HER2 inhibitors COMMON Immunotherapy - CTLA-4 - PD-1/PD-L1 inhibitors
74
What are some nonpharms for diarrhea (4)
- Keep well hydrated - Eat smaller, more frequent meals - Can try BRAT diet - Avoid greasy foods and high fiber content
75
When should cancer patients contact clinic for diarrhea
7+ Loose stools/day ABOVE baseline
76
How to treat Grade 1 diarrhea
Standard diarrhea management - Recommend ORT, stay hydrated - Can take loperamide
77
How to treat grade 2 diarrhea
1. HOLD agent 2. Try loperamide for 3-5 days 3. If ineffective, switch to prednisone PO until return to grade 1 Taper prednisone, Restart checkpoint inhibitor after 1 month
78
How to treat grade 3-4 diarrhea
1. STOP agent 2. Rule out perforation, consider prophylactic antibiotics) 3. Start prednisone PO for 5 days (escalate to infliximab or mycophenolate if no response) Taper the steroid once diarrhea improves -> DON'T restart the checkpoint inhibitor ** No loperamide
79
How to treat Irintotecan diarrhea management (2)
Acute diarrhea (during infusion): - atropine is given prn during treatment Delayed diarrhea (3-4 days after infusion): - HIGH dose loperamide
80
What is regular and high dose loperamide
Regular: - 4mg after first loose BM, 2mg after each subsequent loose BM (MDD 16mg) HIGH dose: - 4mg after first loose BM, 2mg Q2h for 24 hours (MDD 24mg) If unresolved after 24 hours, contact oncology team/ER
81
What is dihydropyrimidine dehydrogenas (DPD) deficiency? What drug is it linked to?
DPD is a rate limiting enzyme in 5-FU metabolism (including Capecitabine) Patients with DPD deficiency who take CAPECITABINE will present with - SEVERE diarrhea, mucositis, neutropenia, neurotoxicity We screen ALL patient prior to initiation (funded by government)

IPFC 6 (16 decks)

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