Myelosuppresion + GI toxicity Flashcards
What conditions do myelosuppresion entail (3)
- Low neutrophils -> neutropenia
- Low RBCs -> Anemia
- Low platelets -> Thrombocytopenia
Treatments that cause myelosuppression
- Radiation
- Cytotoxic chemotherapy
- Monoclonal antibodies
- Targeted agents
Treatments that can cause myelosuppresion
- Radiation
- Cytotoxic chemo
- Monoclonal antibodies
- targeted agents
Why is cancer therapy myelosuppressive in these classes
Cytotoxic chemotherapy
Targeted agents
Anti-CD20
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
Which myelosuppression was the most common DOSE-limiting toxicity associated with chemotherapy
Neutropenia
What are risk factors for neutropenia and its complications
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
What grade of neutropenia would you intervene in and lower dose
Grade 3 or 4
Define febrile neutropenia? Cause?
Defined as a fever for at least an hour and in the setting of neutropenia
- infectious cause
When to treat febrile neutropenia
What to use normally
for low risk
MRSA risk
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
What drug class is given as prophylaxis? when is it given?
G-CSF
(Granulocyte colony stimulating factors)
(filgrastim, pegfilgrastim)
- boosts WBC count
- only give when its curative intent
What risk assessment do you do when giving prophylaxis for FN
Disease type
Chemo regimen
Patient risk factors
Neutropenia with previous cycle
Treatment intent (has to be curative)
Differentiate between Filgrastim and pegfilgrastim
Dose
Start
ADRs (3)
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
What are the benefits of GCSF prophylaxis
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
What patient risk factors are intermediate that you would consider GCSF
- prior chemo or radiation
- Persistent neutropenia
- Bone marrow involvement by tumour
- Recent surgery
- Liver dysfunction
- Renal dysfunction
- Age 65+ receiving full chemo dose intensity
What are other preventative measure of febrile neutropenia
- 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
How does cancer treatment cause anemia? (5)
- Chemo/radiation
- Anemia of cancer (chronic disease) (impaired erythropoietin production/response, impaired iron re-utilization)
- Blood loss
- Nutritional deficiency
- Hemolysis
What are risk factors for cancer-related anemia
- Tumour type
- Stage and duration of disease
- regimen and intensity of tumour therapy (platinum agents known for anemia)
- Presence of infection
- Surgical intervention
What are symptoms of anemia in cancer patients?
Which one is the greatest?
FATIGUE, dizziness, depression
Anorexia, Nausea
Low skin temp, pallor skin
Increased tachy, palipiation
T/F Anemia Fatigue is relieved by sleep or rest in cancer patients
False
What hgb levels does fatigue increase significantly in
<120 hgb
When are RBC transfusions indicated in anemia (2)
- Rapid correction of Hb
- Increase in blood volume
What are drawbacks of using RBC transfusion
- The effect of RBC transfusion are short lived
- It does not address the underlying process of anemia
- There are risks associated with RBC transfusion
What are the ADRs of RBC transfusion
Serious (4)
Mild (2)
Serious ADRs
- Transmission of infection (viral, HIV, hepatitis, bacterial)
- Acute and delayed hemolytic reactions
- Immunosuppression
- Transfuion-related acute lung injury
Mild
- Fever
- urticaria
What erythropoetic agents are used in anemia
Eprex
Longer hald life
- Aranesp
- Darbopoetin
What is the evidence of using erythropoietic agents (2)
- Improves QoL
- decreases # of transfusions used
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
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
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
Which agents cause thrombocytopenia
- Cytotoxic chemo
- BCR-ABL TKIs
- VEGF/VEGFR inhibitors
- PARP inhibitors
- BCL-2 inhibitors
- CDK 4/6 inhibitors
- BTK inhibitors
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
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
What are disease specific risk factors for CINV (5)
- Tumour location: GI, brain, liver
- Fluid/electrolyte imbalances
- Constipation
- Ileus
- Kidney dysfunction
Which drugs are 5HT3 serotonin antagonists (3)
First gen
- Ondansetron
- Granisetron
2nd gen agent
- Palonosetron
What does evidence say of use in Ondansetron (1st gen) vs Palonosetron (2nd gen) in MEC and HEC
Palonosetron is better
What is the indication for 5HT3 antagonists
For ACUTE events for MEC and HEC
What ADRs are associated with 5HT3 antagonists (3)
Headache
Constipation
Transient inc in LFTs
What drugs are substance P/NK1 receptor antagonist (2)
Aprepitant
Netupitant/Palonosetron
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
What does evidence say of palonestron vs Akynzeo (combo of 5HT3 + NK1)
Combo is more effective in acute and delayed
What are ADRs associated with NK1 receptor antagonist (2)
- Fatigue/asthenia (lack of energy)
- hiccups
Which corticosteroids are used in CINV?
What is it synergistic with?
Dexamethasone
- synergistic with 5HT3 (ondansetron)
Indication for corticosteroid in CINV
for prevention of DELAYED CINV
for all MEC and HEC (multi-day with HEC)
What are the ADRs with corticosteroids
- Hyperglycemia
- Psychosis
- insomnia
- dyspepsia
- hiccups
(caution in diabetics)
What are the D2 antagonists used in CINV (5)
- Prochlorperazine
- Metoclopramide
- Domperidone
- Haloperidol
- Olanzapine
What is the indication for D2 antagonists
For BREAKTHROUGH nausea in conjunction with other agents
Can be for prevention in HEC/MEC
What are ADRs of D2 antagonist (3)
- Sedation
- Hypotension
- Extrapyramidal symptoms (affect motor activity)
What are benzodiazepines indicated for in CINV? Which one is used
Lorazepam
Used for anticipatory nausea
- someones for breakthrough in combo
What are cannabinoids indicated for in CINV? Which one is used?
Nabilone
For BREAKTHROUGH nausea (+ help appetite)
- Used as last resort
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)
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)
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)
Sumarize CNIV drugs for LEC (1)
Dexamethasone day of chemo
Sumarize CNIV drugs for Minimal EC (1)
No antiemetics recommended
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
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
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
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)
T/F after mucositis is healed the mucosa appears normal
True
- ONLY appears normal, but significantly altered
- inc vulnerability to future episodes
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
What drug is used for prevention of radiation induced mucositis
Benzydamine 0.15% mouthwash rinse (Q2-3h up to 8x/day)
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
What is used for prevention in HSCT (hematopoietic stem cell transplant) patients
Palifermin
What other therapies are validated by MASCC guidelines for mucositis
Laser therapy
Oral care protocols
What is NOT recommended in MASCC guidelines for mucositis
- Chlorohexidine
- Antimicrobial lozenges
- Sucralfate
- Acyclovir
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
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
What is the efficacy of cryotherapy
Leads to vasoconstriction
- Reduces amount of 5-FU reaching mucosa
50% reduction in frequency of mucositis
What is the efficacy of Palifermin
Mitogenic effect on mucosal epithelium
Reduced incidence AND DURATION of severe mucositis
What are ADRs of palifermin? (5) Most common?
- Rash (most common)
- Edema
- Tingling.itching
- thickness/discolouration of tongue/mouth
- Arthralgias
What is used for prevention of mTOR induced mucositis
Dexamethasone
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
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
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
When should cancer patients contact clinic for diarrhea
7+ Loose stools/day ABOVE baseline
How to treat Grade 1 diarrhea
Standard diarrhea management
- Recommend ORT, stay hydrated
- Can take loperamide
How to treat grade 2 diarrhea
- HOLD agent
- Try loperamide for 3-5 days
- If ineffective, switch to prednisone PO until return to grade 1
Taper prednisone, Restart checkpoint inhibitor after 1 month
How to treat grade 3-4 diarrhea
- STOP agent
- Rule out perforation, consider prophylactic antibiotics)
- 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
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
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
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)
