Chemotherapy-Induced Diarrhoea, Constipation, Mucositis Flashcards
Other predictive factors of CID
- First cycle of chemotherapy
- Cycle duration greater than 3 weeks
- Concomitant neutropenia
- Other symptoms such as mucositis, vomiting, anorexia, or anaemia
Risk factors for CID
- Age greater than 65 years
- Female
- ECOG performance status of at least 2
- Bowel inflammation or malabsorption
- Bowel malignancy
- Biliary obstruction
Potential Causative Agents for Chemotherapy-Induced Diarrhoea
a. Cisplatin/Oxaliplatin
b. Cyclophosphamide
c. Cytarabine
d. 5-FU/Capecitabine
e. Gemcitabine
f. Methotrexate
g. Doxorubicin/Daunorubicin
h. Taxanes
i. Irinotecan/Topotecan
j. Oral Targeted Therapy
MOA of CID
Direct damage and inflammation to mucosa of intestine, which leads to imbalance between absorption and secretion
Severity grading for CID
CTCAE Version 5.0
Grade 1
Increase of <4 stools per day above baseline
Grade 2
Increase of 4-5 stools per day above baseline
Limiting ADL
Grade 3
Increase of ≥7 stools per day above baseline
Hospitalisation needed
Limiting self-care
Grade 4
Life threatening
Urgent intervention needed
Grade 5
Death
Criteria for complicated CID
● Grade 3 or 4
● Grading 1 or 2 with at least one of the following
○ Cramping
○ >Grade 2 N/V
○ Decreased performance status
○ Fever
○ Sepsis
○ Neutropenia
○ Frank bleeding
○ Dehydration
Criteria for uncomplicated CID
Grade 1 or 2
No complicating signs or symptoms
CID goals of therapy
- Decrease morbidity and mortality from CID
- Improve QOL and ADL
- Improve recovery of intestinal mucosa
- Decrease hospitalisation
Management of uncomplicated CID
- Withhold chemotherapy for Grade 2
- Diet modifications
- If diarrhoea persists after 12-24 hours…
When to resume chemotherapy for Grade 2?
When symptoms resolve; consider dose reduction of drug
Diet modifications for uncomplicated CID
a. Oral hydration with 8-10 large glasses of clear liquids
b. Loperamide
c. If diarrhoea improve after 12-24 hours, continue with diet modifications and begin to add solid food
If diarrhoea persists after 12–24 hours
1) Schedule loperamide 2 mg every 2 hours
2) Start oral antibiotics.
3) For diarrhoea that progresses to severe or complicated, treat as such.
4) For diarrhoea that persists as uncomplicated 12– 24 hours after scheduled loperamide, begin octreotide or other second-line agent.
Administration of Loperamide
Loperamide 4 mg by mouth, then 2 mg by mouth every 4 hours or after every episode of diarrhoea. Continue until 12 hours free of diarrhoea, then stop.
Management of complicated CID
1) Withhold chemotherapy
2) Restart at decreased dosage
3) Administer octreotide
4) Start IV fluid hydration
5) Start IV antibiotics
Administration of octreotide
SC 100–150 mcg TDS or
IV with dose escalation up to 500 mcg TDS
MOA of loperamide
Opioid that inhibits smooth muscle contraction of intestine to decrease motility (primary neurotransmitter is acetylcholine)
Adverse effects of Loperamide
a. Constipation
b. Abdominal pain
c. Dizziness
d. Rash
e. Bloating
f. N/V
g. Dry mouth
h. Drowsiness
Which grade does Loperamide has limited efficacy?
Grade 3-4
High dose of Loperamide has been associated with ______.
Paralytic ileus
Maximum daily dose of Loperamide
16mg
MOA of Octreotide
Causes decreased hormone secretion, which
- increases transit time within intestine
- decreases secretion of fluid
- increases absorption of fluid and electrolytes
Adverse effects of Octreotide
- Bradycardia
- Arrhythmias
- Constipation
- Abdominal pain
- Enlarged thyroid
- N/V
- Headache and dizziness
When is Octreotide beneficial?
5-FU and irinotecan-induced CID
Recommended dose of Octreotide
100-150 mcg SC TDS
May increase at 50 mag increments after 24 hours to 500 mcg TDS of continuous IV
Non-pharmacological management of CID
- Probiotics with lactobacillus to prevent
- Diet modification
Diet modification
- Avoid caffeine, alcohol, fruit juice, foods that contain lactose, foods that are spicy or high in fat or fibre, or dietary supplements with high osmolarity
- Up to 10% of patients experience 5-FU–induced lactose intolerance because lactase activity can be lost temporarily
- Lactose-containing foods should be avoided for at least a week after CID has resolved
- Eat small, frequent meals
- BRAT diet (bananas, rice, applesauce, toast)
- More than 3 L of clear fluids containing salt and sugar
- Electrolyte-containing fluids are ideal
Irinotecan-associated diarrhoea MOA
Irinotecan is a selective, reversible inhibitor of acetylcholinesterase leading to a cholinergic response
MOA: inhibits acetylcholine at muscarinic receptor as a competitive antagonist
Management of Irinotecan-associated Diarrhoea
Early (within 24 hours): Atropine 0.25-1 mg (maximum 1.2 mg) SC or IV
Late (after 24 hours): Loperamide
Adverse effects of Atropine
- Insomnia, dizziness
- Tachycardia, blurred vision, dry mouth
- Constipation
Contraindication of atropine
Glaucoma
Symptoms of Constipation
- Bloating/ feeling of fullness
- Cramping or pain
- Gas/ flatulence
- Belching
- Loss of appetite
- No regular bowel movement for ≥2 days
- Straining to have a bowel movement
- Small hard stools that are difficult to pass
- Rectal pressure
- Leakage of small amounts of stool resembling diarrhoea
- Swollen, or distended, abdomen
- N/V
Factors that Increase Risk of Developing Constipation (1)
Lowered fluid intake and dehydration
Factors that Increase Risk of Developing Constipation (2)
Loss of appetite (anorexia)
Factors that Increase Risk of Developing Constipation (3)
Lack of fibre or bulk-forming foods in the diet
Factors that Increase Risk of Developing Constipation (4)
Vitamin or mineral supplements such as iron or calcium pills
Factors that Increase Risk of Developing Constipation (5)
Overuse of laxatives
Factors that Increase Risk of Developing Constipation (6)
Low level of physical activity/alot of bed rest
Factors that Increase Risk of Developing Constipation (7)
Thyroid problems
Factors that Increase Risk of Developing Constipation (8)
Depression
Factors that Increase Risk of Developing Constipation (9)
High levels of calcium or potassium in the blood
Factors that Increase Risk of Developing Constipation (10)
Cancer growing into the large intestine (bowel)/pressing on spinal cord
Factors that Increase Risk of Developing Constipation (11)
- Pain relievers, especially opioid narcotic medicines (morphine/ codeine)
- Chemotherapy drugs (eg. vinca alkaloids – vincristine vinblastine/ vinorelbine)
- Antinausea drugs (ondansetron, granisetron/ anticonvulsant drugs)
Preventing Constipation
- Eat more fibre
- Eat natural laxatives (vegetables, caffeine, prunes)
- Increase physical activity
- Ensure sufficient caloric intake
Managing Constipation
- Stool softeners
- Laxatives
- Promote or stimulate bowel activity
- Increase fibre or product bulk
- Suppository foam that help promote bowel activity - Enemas
When should suppository/enema not be recommended?
When WBC or platelet counts are low → risk of infection or bleeding
Pathophysiology of Mucositis
Damage to mucosa of the oral cavity, pharynx, larynx, oesophagus and GI tract due to cancer therapy
How does chemotherapy/radiation cause mucotitis?
Direct damage to epithelial stem cells
- Tissue response varies by seasonal and circadian changes
- Targeted therapies (eg. cetuximab, bevacizumab, rituximab) and a variety of small-molecule inhibitors have demonstrated the potential to cause a variety of GI toxicities, including mucositis
Epidermal growth factor
Maintain mucosal integrity
- EGFR can be found in the oesophagus and levels are increased in inflamed mucosa
Five stages of mucositis
- Initiation
- Upregulation
- Signalling and amplication
- Ulceration
- Healing
Initiation
- Direct toxicity to cells, tissues and vasculature
- Generation of oxidative stress and ROS
- Increased vascular permeability → accumulation of toxic drugs
Upregulation
- ROS damage DNA → epithelial cell death
- Production of pro-inflammatory cytokines
Signalling and amplification
- Pro-inflammatory cytokines (TNF⍺,
IL1β, IL6) are released - Positive feedback
Ulceration
- Atrophy and mucosal breakdown
- Oxidative stress leads to inflammatory infiltrates
- Macrophages activated by colonising bacteria
Healing
- Proliferation of epithelial cells
- Return of local flora
Grading of Mucositis
0: no evidence of mucositis
1: erythema and soreness
2: ulcers; eating solids
3: ulcers; requires liquid diet
4: ulcers; not able to take PO
API of oracare suspension
Nystatin 125.000U
Tetracycline 62.5mg
Hydrocortisone 5mg
Diphenhydramine 11.5mg/10mL
Administration of oracare suspension
Administer after food, must swallow
Counsel patient that swallowing can help to coat the throat and enter the gut, allowing for full protection (especially for throat ulcers)
What is the antibiotic regimen for complicated CID?
Ciprofloxacin for 7 days
