Cancer Treatment Toxicities Flashcards
What are the facts about chemotherapy induced toxicity? (3)
- Most patients experience side effects
- For most patients, side effects can be controlled
- Many effective drugs and preventative measures can reduce or eliminate side effects
Understanding side effects and how to manage them is important (chemotherapy). Why? (3)
- Reduce anxiety
- Improve Quality of Life (QoL)
- Maintain optimal chemo dose and schedule
Why/how does chemotherapy cause so much toxicity? (3)
- Common mechanism of cytotoxic drug therapy is to attack dividing (growing) cancer cells
- Lack of specificity – attacks rapidly dividing cells
- Damage occurs to healthy cells that have rapid turnover
Adverse events are classified as urgent, short term, and long term - should know the definitions of each.
- Urgent: need to contact cancer clinic / health care team immediately
- Short Term: occur during treatment, can often be managed with symptomatic care strategies or dose adjustments
- Long Term: may occur months to years after treatment stopped, recognition and treatment can be more difficult
What are some examples of urgent adverse events? (11)
- Temperature
- Shivering
- Flu symptoms
- Nose or gum bleeding that doesn’t stop
- Mouth sores that prevent eating or drinking
- Uncontrolled vomiting
- Diarrhea (severe/continued)
- Difficulty breathing
- Chest pain/irregular heart rhythm
- Decreased urination/dark urine
- Anaphylaxis/infusion reaction
What are some examples of short term adverse events of chemo? (12)
- Nausea / vomiting
- Diarrhea / constipation
- Mucositis/stomatitis
- Myelosuppression
- Hair growth alterations
- Weight gain / weight loss
- Taste / smell alterations
- Fatigue
- Hepatic / renal changes
- Cardiac function changes
- Rash / skin changes / nail changes
- Hypertension
What are some examples of long term adverse events of chemo? (10)
- Infertility
- Secondary malignancies
- Heart failure
- Osteoporosis
- Pulmonary fibrosis
- Cataracts
- Peripheral neuropathy
- Hearing loss
- Fatigue
- Endocrine abnormalities
The NCI has a grading scheme for toxicity - what is it used for?
Helps to assess severity of adverse effects for both:
- Individual patients
- Groups of patients (especially clinical trials) undergoing similar or diverse treatments
Should know the NCI side effect grading scheme, Grade 0 through 5.
Grade 0: none
Grade 1: mild
Grade 2: moderate
Grade 3: severe
Grade 4: life threatening
Grade 5 = death
How often does toxicity criteria grade 0-1 have diarrhea?
How about nausea and vomiting?
Diarrhea:
Increase of 2-3 stools a day compared with usual bowel movements
Nausea and Vomiting:
1 episode per day but can eat
How often does toxicity criteria grade 2 have diarrhea?
How about nausea and vomiting?
Diarrhea:
Increase of 4-6 stools per day compared with usual bowel movements or stools during the night
N/V:
2-5 episodes per day; intake decreased but can eat
How often does toxicity criteria grade 3 have diarrhea?
How about nausea and vomiting?
Diarrhea:
Increase of 7-9 stools per day, or unable to control bowel movements or unable to digest food
N/V:
6-10 episodes per day and cannot eat
How often does toxicity criteria grade 4 have diarrhea?
How about nausea and vomiting?
Diarrhea:
Life threatening 10 or more stools per day or very bloody diarrhea ,or the need of IV fluids
N/V:
10 episodes or more per day or requires parenteral support; dehydration
What are some examples of local hypersensitivity reactions? (6)
- Rash
- Urticaria
- Erythema
- Phlebitis
- Pain
- Vein discoloration
What are some examples of systemic hypersensitivity reactions? (6)
- Bronchospasm
- Angioedema
- Hypotension
- Generalized rash
- Pruritis
- Dermatitis
What are some preventative measures for hypersensitivity reactions?
Pre-medications including the combination of a steroid, an H2-antagonist, an antihistamine and/or acetaminophen
Hematologic toxicities of chemotherapy include? (3)
Myelosuppression
1. Neutropenia
2. Thrombocytopenia
3. Anemia
These are the primary dose-limiting toxicity of chemotherapy
What are direct and indirect hematologic toxicities with chemo?
- Direct cytotoxic effects on the myeloid stem cells by reducing bone marrow production and total circulating blood cells
- Indirectly affects the hematopoietic system by altering the bone marrow’s microenvironment and interacting with lymphoid cells
How is chemo-induced anemia managed?
Infusion of packed RBC
(ESAs are not recommended)
How does chemo cause anemia?
Chemotherapy can deplete hematopoietic stem cells and progenitor cells, causing dose-dependent anemia
How does chemo cause thrombocytopenia?
Chemotherapy can have direct cytotoxic effects on stem cells, as well as inhibition of platelet release or platelet apoptosis
How is chemo-induced thrombocytopenia managed? (3)
- Dose adjustment
- Treatment delays
- Platelet transfusion
How is chemo-induced neutropenia managed? (2)
- Dose reduction or treatment delay
- Prophylaxis with GCSFs
Define febrile neutropenia
- Neutrophils
- < 0.5 or <1.0 with a predicted decline to <0.5 within 48 hours - Fever
- Single temperature of > 38.3C or a temperature of > 38C sustained for over one hour)
What are some risk factors for febrile neutropenia? (4)
- Cytotoxic agent
- Dose intensity of the regimen
- Concomitant chemoradiation therapy
- Severity and duration of neutropenia, patient factors
Febrile neutropenia is a medical emergency. How should it (and shouldn’t it be managed)? (3)
- Seek medical attention immediately
- DO NOT take acetaminophen, ibuprofen or ASA until have contacted a healthcare provider
- Treat empirically with broad spectrum antibiotics
What is empiric antibiotic treatment for febrile neutropenia? (5)
Monotherapy with Anti-pseudomonal beta lactam:
1. Piperacillin-tazobactam
2. Cefepime
3. Meropenem
4. Ceftazidime
OR
5. Vancomycin (or linezolid) if there is a high suspicion of gram positive involvement
How to prevent infection in patient with chemo-induced neutropenia? (5)
- Good hygiene – wash hands frequently
- Protect your skin
- Avoid cuts and scrapes, clean wounds
- Use sunscreen - Reduce exposure
- Avoid crowded places and contact with people who are sick
- Avoid sharing food, dishes and personal items - Good mouth care
- Care of medical devices (iv lines, catheters)
What is the medication combo used for chemo-induced neutropenia?
Filgrastim and Pegfilgrastim
- Myeloid growth colony stimulating factors (G-CSFs)
- Regulates release, promotes proliferation and differentiation of myeloid cells, including neutrophils
When is primary and secondary prophylaxis used for chemo-induced neutropenia? (3)
Primary prophylaxis:
- Used empirically for patients at 20+% risk for febrile neutropenia
Secondary prophylaxis:
- Prevent recurrence after experiencing febrile neutropenia from a previous chemo cycle
- To shorten the duration of severe neutropenia in patients who experienced neutropenia without fever in a previous chemo cycle
How does GI mucosal toxicities happen from chemo?
Due to rapid turnover of the epithelial lining of the GIT
What are the risk factors for GI mucosal toxicities from chemo?
Continuous chemo infusions and concurrent radiation therapy
How does chemo and radiation cause mucositis (mouth sores)?
Reduce mucosa regeneration
- Hyposalivation
What are the consequences of mucositis (mouth sores)? (4)
- Painful
- Limited nutritional intake
- Affect outcome – dose reduction, delay, or stop treatment
- Potential site for infection
How to prevent mucositis? (3)
- Good oral hygiene
- Brush with a soft toothbrush, gentle flossing, moisture rinses
- Avoid irritating foods (e.g. orange juice, tomatoes)
- Make sure dentures fit - Salt/Baking Soda/Normal Saline Rinse
- Rinse 3 to 4 times daily
- Avoid alcohol containing commercial mouthwash - Ice Chips
- Chewing 30 minutes prior to chemotherapy may help
- Contraindicated with some chemotherapy regimens
How is mucositis treated? (4)
- Prescription mouth wash
- Steroids
- Local anesthetics
- Topical analgesics - Fungal infection (e.g. thrush)
- Nystatin
- Fluconazole (oral) - Analgesia
- Severe symptoms
- Hospitalization
- IV narcotics
- Parenteral nutrition
‘Koolstat’ and ‘Magic Mouthwash’ for mucositis treatment - yay or nay?
Nay
1) NOT evidence-based medicine and is INEFFECTIVE for treating oral thrush and pain associated with oral mucositis
2) Expensive for both the patient and healthcare system
3) Risk of Nystatin resistance
4) Risk of steroid causing oral thrush
5) Risk of causing harm to our patients
Dyspepsia/Heartburn/Stomach pain is often a side effect of?
Supportive care medications - e.g., dexamethasone, antibiotics
Dyspepsia/Heartburn/Stomach pain can be managed how? (3)
- Avoid aggravating factors (e.g. tobacco use)
- Dyspepsia medications – H2blockers, PPIs, antacids
- May use treatment in various ways depending on symptoms e.g. regularly close to treatment then prn
How might diarrhea be managed non-pharmacologically? (5)
- Small, frequent meals, frequent hydration
- Limit caffeine, fried, greasy foods, foods high in lactose or sorbitol
- Avoid foods high in insoluble fiber
- Encourage foods high in soluble fiber (bananas, applesauce)
- Avoid excess hyperosmotic liquids (pop, juice)
How is diarrhea managed pharmacologically? (3)
- Rule out infectious causes
- Loperamide or diphenoxylate
- Opioid analogues, reduce gut motility, reduce fluid secretion - Octreotide
- Somatostatin analogue, reduces fluid secretion from the stomach and intestine, increases fluid reabsorption from the intestine
Irinotecan can cause acute or delayed diarrhea. Should know the mechanism and treatment for acute (3)
- Cholinergic mechanism – may be severe
- Other cholinergic symptoms: flushing, cramping
- Use atropine 0.3 – 0.6 mg IV/SC to prevent and/or treat (repeated up to maximum dose of 1.2 mg)
Irinotecan can cause acute or delayed diarrhea. Should know the mechanism and treatment for delayed (3)
- Secretory diarrhea – thought to be due to abnormal ion transport across injured intestinal mucosa that leads to increased water and electrolytes in GI tract
- May be life threatening; occasionally fatal
- All patients must be carefully educated
Should know the intensive loperamide regimen for irinotecan induced diarrhea (5)
- Two tablets (4 mg) at first onset of diarrhea
- Followed by one tablet (2 mg) scheduled every 2 hours during the day
- During the night, two tablets (4 mg) every 4 hours
- Take until diarrhea free for 12 hours
- Seek medical attention if no resolution within 24 hours
How might constipation be caused by chemo/radiation? (3)
- Supportive care treatment side effect
- e.g. ondansetron, opioids - Chemo-induced
- Reduction in GI motility
- More water reabsorbed from the GIT - Radiation to GIT
What are the consequences of constipation? (4)
- Pain and discomfort
- Increased nausea
- Bowel obstruction
- Hospitalization
What are the non-pharm management options for constipation? (4)
- Increase fluid intake – at least 1.5-2 liters
- Physical activity as tolerated
- Promote fiber intake
- Minimize alcohol and caffeine intake
What are some pharmacological management options for constipation? (3)
- Stimulants (onset 6-12 hours)
- Senna – start 1-2tabs hs, max 4 tabs po BID
- Bisacodyl – start 5mg hs, max 15mg po TID - Osmotic (onset 1-3 days)
- Lactulose – start 15ml po od, max 60ml po TID
- Polyethylene Glycol – 17-34g od, max 34g po TID - Enemas, suppositories
What are some warning signs to look out for with constipation? (4)
- No bowel movement for 3 to 5 days
- Not passing gas
- Blood in stool (or black tar like stools)
- Foul smelling vomit
What to know about alterations to taste and smell in chemo? (4)
- May lead to reduced appetite & weight loss
- May affect taste by direct taste receptor stimulation due to secretion of the drug in saliva or via gingival crevice fluid
- Often described as a metallic or chemical taste when chemotherapy is delivered
- Taste changes may persist after drug clearance due to damage to the taste buds; as well as psychological effects
What are some cutaneous reactions to chemo that you should know? (4)
- Photosensitivity :
- Exaggerated by UV light; sunburn, blistering
- Minimize sun exposure; use effective sunscreen greater than or equal to SPF15 - Nail changes
- Hyperpigmentation
- Dry skin, rashes
Hand foot skin reaction (HFSR) is most commonly encountered with which drug?
What are some other drugs that can cause it? (4)
Most commonly:
1. Capecitabine
Also with:
2. Liposomal doxorubicin
3. Continuous 5-fluorouracil infusions
4. Everolimus
5. Lapatinib
Weirdly enough, HFSR has correlation with treatment response. Meaning? (3)
- Appears to be correlation in development of SE and the pts treatment response. Pts who develop this SE tend to have better treatment outcomes than pts who don’t experience this SE.
- Improvements in progression free survival and overall survival.
- Similar correlations found in capecitabine use in breast cancer pts and colorectal pts.
What to know about HFSR prevention and treatment?
Prevention is key because there is NO treatment
What is the prevention strategy for HFSR? (5)
- Avoid exposure to heat
- Washing dishes in luke warm water
- Avoid prolonged hot baths or showers - Protective gloves and socks
- Moisturizer to hands and feet - BID
- Avoid activities that apply pressure to skin of hands and feet
- Avoid fragrances
What hair changes are associated with chemo? (5)
- Alopecia
- Scalp hair loss is the most common area as this hair grows most rapidly
- Eyebrows, eyelashes and other slow growing facial and body hair can be affected - Depigmentation
- Change of color
- Change of texture
- Eyelash and eyebrow changes
What are 3 chemo drugs that have very high rates of alopecia?
- Doxorubicin
- Paclitaxel
- Docetaxel
What are some chemo drugs that have low risk for hair loss? (5)
- 5-fu
- Capecitabine
- FOLFOX
- FOLFIRI and CMF
- Many of the oral targeted agents
What are some chemo agents that can cause neurotoxicity? (4)
- Platinum agents
- Taxanes
- Vinca alkaloids
- Proteosome inhibitors and immunomodulating agents
What are some ways in which neurotoxicity can manifest? (3)
- Most commonly manifested as peripheral neuropathy
- Ototoxicity: tinnitus and hearing loss
- Autonomic neuropathies:
- Abdominal cramping
- Constipation (paralytic ileus)
- Myalgias
- Gait disturbances
- Cranial nerve neuropathy
What are the symptoms of peripheral neuropathy? (15)
- Pain (constant or transient, shooting or stabbing)
- Burning
- Tingling (“pins and needles” feeling)
- Loss of feeling (numbness or less ability to sense pressure, touch, heat, or cold)
- Trouble using fingers to pick up or hold things; dropping things
- Balance problems
- Trouble with tripping or stumbling while walking
- Pressure may hurt more than usual
- Temperature may hurt more than usual (mostly cold; this is called cold sensitivity)
- Muscle weakness
- Trouble swallowing
- Constipation
- Trouble passing urine
- Blood pressure changes
- Decreased or no reflexes
What are some potential treatments for peripheral neuropathy? (3)
- Antidepressants
- Opioids
- Anticonvulsants
Chemo has increased risk of developing cardiovascular complications. The risk is greater when?
If there is known history of heart disease:
- Arrhythmias
- Myocardial necrosis causing dilated cardiomyopathy
- Vasospasm or vaso-occlusion resulting in angina or myocardial infarction
- Pericardial disease
What is the MOA of anthracyclines in causing cardiotoxicity?
Reactive free radical formation causing damage to myocardial cells
True or False? Anthracyclines can be used indefinitely
False - dose-dependent - lifetime maximum doses
What kind of heart injury can anthracyclines cause? (2)
- Direct injury to heart, either acutely (MI, arrhythmias) or in a delayed or chronic fashion (CHF)
- Delayed cardiomyopathy - dose related and irreversible
What is the 2nd most common cause of chemo-related cardiotoxicity after anthracyclines?
Fluorouracil
How does trastuzumab hurt the heart? (3)
- Associated with decreased left ventricular ejection fraction (LVEF), congestive heart failure, arrhythmias, hypertension, cardiomyopathy and death
- More pronounced if given concurrently with an anthracycline – not recommended
- Reversible with discontinuation of treatment and initiation of standard cardiac medications
