Prevention and Management of Anti-Neoplastic Adverse Effects Mucositis, Hand&Foot, Alopecia, Infusional Reactions, Constipation Flashcards
CTCAE (Common Terminology Criteria for Adverse Events)
◦ The CTCAE is a descriptive terminology utilized for adverse event (AE)
reporting developed by the National Cancer Institute (NCI)
◦ Incorporates a grading (severity) scale for each Adverse Event Term
Grade 1 Mild
• Asymptomatic or mild symptoms
• Clinical or diagnostic observations only
• Interventions not indicated
Grade 2 Moderate
• Minimal symptoms
• Local or non-invasive intervention indicated
Grade 3 Severe
• Severe or medically significant (but not immediately life– threatening symptoms
• Hospitalization or prolongation of hospitalization
indicated
Grade 4 Life threatening
• Life threatening consequences
• Urgent intervention indicated
Grade 5 Death • Death related to the adverse effect
Mouth Related Side Effects
Mucositis
◦ Small sores (ulcers) in the lining of the mouth or throat
Taste Changes
◦ Choose food that tastes good
Dry Mouth
◦ Sip water, mouth moisturizer (biotene, oralbalance), sugarless mint or gum (xylichew or excel)
Dry, Cracked, Lips
◦ Water based lip care product (eg. blistex)
◦ Avoid petroleum based lip balm (eg. lypsyl, vaseline, chapstick) (Doesn’t promote healing of lips as well)
Thick saliva
◦ Thick saliva and secretions can contribute to feeling unwell
Cavities
◦ Risk is increased if reduced saliva or reduced oral hygeine
Good mouth care very important
Oral Mucositis
◦ An acute inflammation and/or
ulceration of the oral or oropharyngeal
mucosal membranes. It can cause
pain/discomfort and interfere with
eating, swallowing, and speech.
Causes:
◦ Radiation
◦ head, neck, or salivary glands
◦ Total body irradiation
◦ Chemotherapy
◦ Continuous or high dose chemotherapy increases risk
◦ Hematopoietic Stem Cell Transplantation (HSCT)
Risk Factors for Mucositis
Xerostomia
◦ Decrease or thickening of saliva is common with cancer treatments
◦ Medications that cause xerostomia:
◦ Anticholinergics
◦ Opioids
◦ Antihistamines
◦ Consider artificial salivary replacement if needed.
Oral health
◦ Periodontal disease
◦ Poor fitting dentures
◦ Poor oral hygiene
Dehydration
Alcohol/tobacco use
O2 therapy
Why is mucositis such a big deal?
◦ Pain
◦ Discomfort
◦ Malnutrition/dehydration because hurts to swallow/eat/drink
◦ Infection
◦ Open sore allows entrance of bacteria
◦ Treatment
◦ Severe mucositis may lead to treatment delays to allow sores to heal. Treatment delays can compromise
treatment outcomes
Prevention of Mucositis
Good oral hygiene
◦ Extra soft toothbrush, no scrubbing!
◦ Rinse brush under warm water to soften bristles
◦ Floss daily, UNLESS causes pain/bleeding or plts < 50
◦ If dentures, brush/rinse after every meal and allow long periods without wearing
dentures (ie overnight)
◦ Alcohol Free Chlorhexidine Rinse:
◦ Directions: Swish 15 mL in your mouth undiluted for 30 seconds, then spit out. Use after breakfast and before bedtime, avoid eating or drinking for approximately 30 minutes after its use.
Bland mouth rinses (alcohol free!) after all meals
◦ Normal Saline (1/2 tsp salt in 8oz of water
◦ Club soda or Sodium Bicarbonate (1 tbsp. in 2 cups of water) after add ¼-1/2 tsp or baking soda, swishing feels nice
Extra Dental Precautions IF Head/Neck radiation treatment:
◦ High fluoride content toothpaste (5000ppm) used twice daily e.g. Prevident 5000 plus (prescription)
◦ Fluoride trays – Use for 10 minutes every day before bed
Cryotherapy
◦ For chemotherapy highly associated with mucositis, patients may be instructed to hold ice chips, popsicles, or cold water in mouth five minutes prior, during, and for 30 minutes after the infusion
◦ Don’t use with Oxaliplatin!!!!! (neuropathy)
it keeps circulation around area low and less chemo getting to that area
AVOID the following:
for mucositis
◦ Commercial mouthwashes which contain alcohol (including chlorhexidine
rinse that contains alcohol)
◦ Hard, acidic, extremely hot, salty or spicy foods because these can irritate
the tissues
◦ Poorly fitting dentures
◦ NOTE- patients may experience weight loss and hence may need to have their dentures refitted
during treatment
◦ Caffeine, alcohol, tobacco
Treatment of Grade 1-2 Mucositis
Measures already discussed…. PLUS:
Increase use of bland rinses
◦ Every 1-2 hours if needed
Benzydamine HCl Rinse (alcohol free)
◦ sometimes used for radiation induced mucositis
Pain control
◦ Systemic analgesics
◦ Topical anesthetics
Monitor for infection
◦ Open sore and entry for bacteria, refer if suspect infection
◦ Patients can also develop thrush/candidiasis. Treat appropriately.
Monitor for bleeding
◦ Open wounds can begin to bleed, refer for excessive bleeding
Frequent sips of water for xerostomia
Treatment of Grade 2-3 Mucositis
Measures already discussed PLUS:
Can switch from a toothbrush or an oral sponge to clean mouth
Pink Ladies
Akabutus mouthwash
Dr. Akabutus or “Magic” Mouth Wash
Compounded mouth-rinse that is commonly used in Alberta for mild-moderate mucositis from
antineoplastic therapy.
Akabutu’s mouthwash AHS cancer care recipe (however many other recipes exist):
◦ Nystatin 100,000 unit/ml 42 ml prevent thrush
◦ Lidocaine HCL Viscous 2% 50 ml
◦ Sodium chloride 0.9% 200 ml
◦ Hydrocortisone 10 mg x 5 tabs reduce inflamm
◦ glycerin 100% 4 ml
Directions for use:
◦ Swish/gargle 15-30 ml in mouth/throat x 1 minute (spit out excess), q4-6h prn. Avoid eating or drinking for
approximately 30 minutes after its use.
Used OFTEN but somewhat controversial and evidence is lacking
◦ Efficacy may not be better than saline
◦ May not shorten healing time
◦ Expensive
◦ Sub-therapeutic level of nystatin – risk of resistance
◦ Corticosteroid could increase risk of thrush
Pink Lady
Compounded product:
◦ Equal parts Lidocaine viscous 2% oral solution and Aluminum hydroxidemagnesium hydroxide (Maalox, Almagel or equivalent)
Swish/gargle 15 ml in mouth/throat x 1 minute (spit out excess), q4h prn
Best used 20 mins prior to meals
CAUTION: systemic side-effects of lidocaine, including fatal arrhythmia
Severe Mucositis (grade 3-4)
Management suggestions already discussed, PLUS:
Local pain control: May consider adding:
◦ TOPICAL opioid mouthwash (compounded)
◦ e.g. 0.2% morphine mouthwash (i.e. morphine diluted in water to 2 mg/ml)
◦ hold 10 ml in mouth next to painful areas for 2 mins then spit out, q4h prn
◦ Caution: SHOULD NOT BE SWALLOWED! Each 10 ml of the rinse contains 20 mg morphine!!!
◦ Lidocaine viscous 2% (undiluted)
◦ 15 ml swish x1 minute and spit, or for pharyngeal mucosistis gargle and spit/swallow, q3h prn
◦ CAUTION if swallowing!!!!
◦ Tetracaine 0.5% lollipops
Systemic Pain Control
◦ May need opioids
◦ Grade 4 patients will be hospitalized (remember this is life threatening) and
will usually get a “PCA” (patient controlled analgesia) of IV opioids
Complications:
◦ Infection - sores are really big
◦ Remember they have open sores that can be an entrance point for microbes
◦ Culture, and systemic antibiotics as appropriate
◦ Persistent Bleeding
◦ Malnutrition
◦ IV hydration, enteral or parenteral nutrition
Other Treatments of Oral Mucositis
Dexamethasone 0.5mg/5mL (alcohol free)
◦ for patients on everolimus
Doxepin 0.5% mouthwash (alcohol free)
◦ May be effective for pain (swish and spit)
Hand/Foot Syndrome
Antineoplastic adverse effect characterized by redness and pain on the
palms of the hands and/or soles of the feet
Also called palmar-plantar erythrodysesthesia (PPE)
Commonly associated with the following agents:
◦ Capecitabine (classic example)
◦ Recall Colo-Rectal Cancer lecture with discussion of capecitabine
◦ Fluorouracil (5-FU)
◦ Sorafenib
◦ Cytarabine
◦ Docetaxel and Paclitaxel
Hand/Foot Syndrome or PPE
Predisposing or Aggravating Factors:
◦ Age > 65 years
◦ Female sex
◦ Friction (especially to hands and/or feet)
◦ Manual labour, vigorous exercise, vigorous gardening
◦ Heat
◦ Hot baths/showers, hot weather
◦ Excessive alcohol use
Why is hand/foot syndrome a big deal?
◦ Increased risk of altered skin integrity (lead to infection)
◦ Can ultimately limit the use of a potentially effective therapy for cancer
◦ Can impact treatment outcome
◦ Can reduce quality of life
◦ Can be painful
◦ Impair mobility or ability to do daily self care or recreational activities
Patient Education for Prevention of PPE
Skin care/hygiene
◦ Wash hands/feet with lukewarm water (NOT hot)
◦ Pat dry (DON’T rub)
◦ Apply unscented emollient creams or lotions liberally, gently and often
◦ Avoid sun exposure
Avoid heat
◦ Avoid hot water, saunas, heating pads
◦ Avoid rubber gloves for washing dishes as it intensifies heat (warm water)
Foot Care:
◦ Wear comfortable and well fitting shoes
◦ Avoid going barefoot (wear slippers indoors)
◦ Avoid footwear that is too loose or too tight
Hand Care:
◦ Avoid immersing hands in chemicals (cleaning agents, bleach etc)
◦ Avoid activities or mechanical stress on hands (examples – harsh clapping, tight gripping of tools)
Examples of Gentle Creams for PPE
Bag Balm®
Glaxal Base®
Aveeno®
Lubriderm®
George’s Cream®
Lanolin creams
Patient Self Monitoring
Patient to assess their skin daily for
◦ tingling or numbness
◦ swelling or tenderness
◦ dry furrowed skin that becomes reddened (caucasian patients) or darker (non-white patients)
Note that the first symptom is often tingling and/or numbness of soles/palms
Management of PPE
Pain:
◦ Oral analgesics (example acetaminophen or NSAIDs)
◦ Topical corticosteroids
◦ Cool packs (not direct ice) on palms of hands or soles of feet may alleviate pain.
Alternate on and off for 15 to 20 minutes at a time.
PPE Treatment:
◦ Emolients as discussed
◦ Preliminary data for possible role of oral dexamethasone or celecoxib
Wound care
◦ If skin erosions
If symptoms are severe, may require antineoplastic dose reduction, treatment
delay, or discontinuation
Alopecia
Hair follicles possess rapidly dividing cells and are very
susceptible to the cytotoxic effects of traditional antineoplastic agents
Agents most commonly associated with alopecia are
cyclophosphamide, anthracyclines, taxanes (paclitaxel or docetaxel) etoposide
Can affect many kinds of body hair:
◦ Scalp (most common)
◦ Eyebrows and/or eyelashes
◦ Men’s facial hair
◦ Body hair
◦ Pubic hair
Alopecia implications
Amount and/or extent of hair loss is variable
◦ Thinning to baldness
◦ Scalp most common, but can be other areas or all areas
Implications
◦ Although it is temporary, this can be a devastating side effect for patients
◦ Self image
◦ Patients may see themselves as a “sick person” or “unattractive”
◦ Sexual health
◦ Patients may see themselves as “undesirable” or looking pre-pubescent
Patient Education - Alopecia
Important to have a conversation about this!
Hair loss:
◦ Can begin as early as 1-3 weeks after first treatment but can occur later or
very gradual
◦ Temporary
◦ Will usually begin to grow back 6-8 weeks after last treatment
◦ May grow back different color or texture
◦ Can be messy for patients
◦ May consider a drastic hair cut to ease into the change
◦ In Alberta, a wig can be subsidized if written by prescription
◦ Important to protect scalp from the sun (this skin is sensitive!)
◦ Important to cover head in the winter (substantial loss of body heat)
Hypersensitivity/Infusion
Reactions
Symptoms
◦ Local: localized rash, uticaria, phlebitis
◦ Systemic: dyspnea, bronchospasm, chest discomfort, chills, rigors, fever,
angioedema, hypotension, tachycardia, generalized rash
Commonly associated with:
◦ Taxanes (paclitaxel, docetaxel)
◦ Platinums (cisplatin, carboplatin, oxaliplatin)
◦ Bleomycin
◦ Monoclonal antibodies (rituximab)
Most commonly occur:
◦ with first dose (or first few cycles)
◦ first few minutes to hours, but can be up to 48 hours later
Hypersensitivity/Infusional
Reactions
Prevention:
◦ Each medication that is high risk of hypersensitivity reaction has its own
recommendations (recall docetaxel in breast ca lecture)
However, preventative measures usually incorporate one or more of the following:
◦ Systemic Corticosteroids (Hydrocortisone IV, prednisone PO,
Dexamethasone IV or PO)
◦ H1 antagonist (diphenhydramine, loratidine)
◦ H2 antagonist (ranitidine)
◦ Antipyretic (acetaminophen)
If hypotension is a concern, then common to ask patients on anti-hypertensive agents to hold their antihypertensives for 24 hours pre-infusion.
Hypersensitivity/Infusional
Reactions
Monitoring:
◦ Close monitoring, especially during a first time infusion, is critically important
◦ BP, HR, Temp, O2 saturation
◦ Patient symptoms (chest tightening, airway, malaise)
◦ Some agents have slower infusion rates for first dose (rituximab)
◦ If hypersensitivity reaction occurs, stop/interrupt infusion and initiate supportive
care with corticosteroids, antihistamines, antipyretics, oxygen as required/indicated
◦ Depending on agent, if mild to moderate reaction may rechallenge with additional
premedications and possible reduced infusion rate
◦ If life threatening reaction, offending agent may need to be permanently
discontinued.
Constipation
A subjective experience of unsatisfactory defecation – infrequent stools
or difficult stool passage
Commonly associated with the following cancer related medications:
◦ Vinca alkaloids (Vincristine, Vinblastine, Vinorelbine)
◦ 5-HT3 antagonists (Ondansetron, Granisetron)
◦ Opioids
Constipation
Why is constipation a big deal?
Uncomfortable
◦ Fecal impaction, bowel obstruction, bowel perforation
◦ Hemorrhoids, rectal tearing, fissures lead to bleeding (consider patients may
have a low platelet count)
Patient Education – Constipation Prevention
Encourage:
◦ adequate fluid intake
◦ physical activity and mobilization (as appropriate)
◦ high fibre foods and food laxatives (if not currently constipated)
◦ Prunes, dates, etc
◦ MUST have adequate fluid intake
◦ good toileting habits
◦ attempts to defecate 30-60 minutes after meals to take advantage of gastracolic reflex
Avoid:
◦ Excessive straining (can lead to hemorrhoids, fissures, bleeding)
◦ If receiving myelosuppressive chemotherapy, avoid suppositories, enemas, rectal exams due to low
platelet count or neutropenia (bleeding or infection)
Monitor bowel movement frequency, stool appearance and effort to defecate
◦ If not bowel movement in 3 days, may need pharmacotherapy
◦ Contact team if constipation with severe pain, distention, cramping (possible obstruction)
◦ Contact team if sensory loss and motor weakness (possible spinal cord compression)
Constipation Management
Rule out a bowel obstruction – Warning signs are:
◦ Patient cannot pass gas
◦ Sudden watery diarrhea after constipation
◦ Seek medical attention if suspected obstruction
Oral laxatives
◦ Sennosides
◦ Start with regular dosing and then progressively increase until normal bowel pattern restored and movements are soft and comfortable to pass
◦ PEG 3350
◦ Commonly used if sennosides are too harsh or cause cramping
◦ May take 2-3 days to take effect
◦ Can start at once daily but can increase to twice daily or higher if required
Rectal products
◦ May consider if patient is not at risk of neutropenia or thrombocytopenia (suppository, enema)
If constipation with previous chemotherapy cycles, consider pre-emptive laxative
use with PEG 3350
