Nutritional Complications of Anti-cancer Therapy (Week 6 Lecture 2) Flashcards
How is nutritional compromise commonly observed in cancer patients?
- weight loss
- anorexia
- malabsorption
- maldistribution of fat and lean body masses, including liver and muscles
What results in nutritional compromise?
- cancer
- malabsorption
- surgery
- radiation
- systemic therapy
How does cancer result in nutritional compromise?
- Production of inflammatory mediators leading to catabolism of muscles and fat.
- Decrease in intake due to dysphagia and early satiety.
How does systemic therapy result in nutritional compromise?
Classical cytotoxic chemotherapy
Targeted agents to
* Extracellular domain of receptor
* Intracellular kinases
* Other parts of the intracellular domain- allosteric
Immunotherapy:
* Cytokines
* Immune cell: Activator and Anti-suppressors.
What is indirect nutritional complications?
Nutritional derangement arising from non-specific side effects of anti-cancer therapy, including:
* Dysgeusia
* Anorexia or early satiety
* Nausea and vomiting
* Mucositis and esophagitis
* Diarrhea
* Malabsorption.
* hyperlipidemia
* hyperglycemia
* hypothyroidism
Grading of toxicity
The NCI-CTCAE criteria is a standardized language for grading of toxicity or symptoms from cancer and therapy (universal language). From grade 1-5 i.e. mild to fatal.
* Not all toxicity or symptoms or laboratory finding have all 5 grades.
* If the term is not found, then use grade 1-5 or mild, moderate, severe or fatal.
* Currently, we are using version 5.1.
Describe the complication of dysgeusia?
Change in taste, often described by patients as metallic taste Leading to change in what type(s) of food that they will eat.
* A result of decrease in the number of taste buds
* Common side effects of many chemotherapeutic agents.
* Recently, NTRK inhibitors interfere with NTRK2 in central nervous system
Grading for dysgeusia
- 1: altered taste and no change in diet
- 2: altered taste with change in diet, including oral supplement; noxious or unpleasant taste or loss of taste
Describe the nutritional complications of nausea and vomiting
- Decrease in intake
- Avoidance to eat.
- Is a combination of change in smell perception, change in taste perception, activation of the vomiting centre in the brainstem.
- drugs cause most nausea and vomiting of anything
Grading for nausea
Grading for vomiting
Nutritional complications of anorexia/ early satiety
Feeling full in the stomach earlier than expected, leading to total reduction of food intake or preferential food intake.
Causes of anorexia/ early satiety other than chemotherapy
- Obstruction of gastric outlet or duodenum
- Inflammatory mediators of cancer
- Delay in gastric emptying.
Grading for anorexia
What is mucositis?
Inflammation of the mucous membrane (sores)
Where is mucositis observed?
Chemotherapy: up to 40%
* Breast cancer
* Colorectal cancer
* Head and neck cancer
Bone marrow transplantation: up to 75%.
Radiation therapy in
* Head and neck (especially back of mouth)
* Upper esophagus.
Fungal overgrowth by Candidia spp. due to steroids (goes into blood stream)
grading for oral mucositis
Describe esophagitis
inflammation of esophagus
What results in esophagitis?
- Chemotherapy and radiation: direct damage of the mucosa (Esophagus, Lung, Larynx)
- Fungal infection by Candida spp.
- Viral infection by CMV, HSV.
- Reflux due to steroid.
Grading for esophagitis
What results in malabsorption?
- Resection of part of bowels
- Radiation
- Chemotherapy
resection of bowel parts causing malabsorption
- Gastric resection: decrease in food transit time into small bowel, leading to dumping syndrome, malabsorption and osmotic diarrhea.
- Small bowel: usually after a large portion resection or damage of the epithelial cells/crypts of Langerhan, leading to malabsorption and osmotic diarrhea. (60-80% substantial problem)
- Pancreas: Loss of pancreatic enzyme for digestion, thus malabsorption and osmotic diarrhea.
Radiation causing malabsorption
Mucosal damage leading to a combination of malabsorption and secretory diarrhea.
Chemotherapy causing malabsorption
Agent dependent; commonly observed in:
* Chemotherapy for colorectal cancer: Irinotecan, oxaliplatin, capecitabine and 5-FU. Leading to inflammation and/ulceration of mucus membrane and secretory diarrhea.
* Novel anti-cancer agents: epidermal growth factor targeting agents and anti-cytotoxic T-lymphocyte antigen antibody (anti- CTLA-4). Secretory diarrhea versus inflammation/ulceration.
* Notch inhibitor: globet cell hypertrophy, leading to secretory diarrhea.
Grading for malabsorption
What results in diarrhea?
- Chemotherapy (irinotecan, 5-FU): Damage of the crypts in the small bowels, leading to secretory diarrhea and decrease in absorption of the electrolytes
- Immunotherapy and radiation: direct damage to both the crypts and the mucous membrane
- Targeted agents (EGFR TKI; VEGFR TKI): drug induced dysfunction of the Na/K ATPase of the ion channels, leading to reduction of sodium uptake
Grading for diarrhea
What may result in hyperlipidemia?
- Aromatase inhibitor for treatment of breast cancer: Aromatase is the enzyme for the conversion of androgen to estrodial and estrone in either the ovaries or peripheral fat (2 classes: steroidal and non-steroidal)
- Bexarotene: a retinoic acid derivative for the treatment of cutaneous T-cell lymphoma leading to rapid and high elevation of TG, VLDL, LDL and total cholesterol by depositing fat in liver so it does not mobilize in blood and other tissue.
- Alectinib and lorlatinib: ALK inhibitors for NSCLC (non-smoker lung cancer): Mechanism unknown.
- mTOR inhibitors for RCC causing decrease in LPL leading to hypertriglyceridemia and decrease in LDLr so increase in LDL.
Grading for hyperlipidemia
What results in hypothyroidism?
- Hypothyroidism associated with anti-angiogenic therapy observed as primary hypothyroidism with elevation of TSH and normal to low T3 or T4.
- Thyroid dysfunction with formation of auto-antibody to thyroid producing cells, leading
to thyroiditis (more common to be hypo than hyper)and can lead to destruction of the pituitary gland (multiple endocrine organ dysfunction)
Grading for hypothyroidism
What results in hyperglycemia?
- Hyperglycemia due to autoimmune mechanism: destruction of the Islet cells by auto-antibody
- Altered glucose metabolism
What might cause altered glucose metabolism?
- Exaggerated glucose response after glucose administration
- Decrease in insulin sensitivity via decrease in number and size of Islet cells
- Decrease in insulin clearance by liver
- Increase in gluconeogenesis via increase in gluconeogenic gene expressions.
Grading for hyperglycemia
What results in fatty liver?
Most common cause of cirrhosis in N. America/W Europe. Observed in 5-FU and irinotecan treated colorectal cancer patients.
* 5-FU: Mitochondrial collapse leading to impairment of oxidation of fatty acids. The reactive oxygen species (ROS) from fatty acid accumulate in hepatocytes.
* irinotecan: Possibly through inhibition of mitochondrial membrane and mitochondrial oxidation and electron transfer along the respiratory chain, resulting in production of ROS.
general medical management of nutritional complications
Education:
* Patients and family
* Nursing and dietitians
* OURSELVES.
Monitoring:
* General dietary questions
* Physical examination
* Laboratory investigations: Ca, glucose, TSH, albumin
* Scans for sarcopenia.
Management of dysgeusia
- No direct medications have been proven useful, but use of lemon juice, zinc supplementation is commonly used.
- Change of food strategies: Use of blend food, frequent small meals, high protein diet.
Management of nausea/ vomiting
- medication for moderate/high
- medication for low day 1 pre-chemo
Management of mucositis & esophagitis
Early recognition and intervention with
* Topical anesthetics
* Anti-fungal for suspicious of fungal infection
* keratinocyte growth factor (stimulates skin growth) in bone marrow transplant patients
Management of anorexia
- nutritional supplementation: protein intake, EN vs. PN
- Appetite stimulants: steroid, cannabinoid, anti-depressant
Management for hyperlipidemia
- Diet modification as advised by the Canadian Heart Association.
- Pharmacological intervention: HMG co-A inhibitors
- Exercise.
Management of diarrhea
Chemotherapy, radiation or targeted agents:
* Fluid intake
* Diet modification: BRAT diet- banana, rice, apple sauce and bread and avoid greasy and spicy food.
* Pharmaceutical
Immunotherapy related diarrhea/colitis:
* Anti-diarrheal
* Corticosteroid
* if not resolved, GI consult for endoscopy to prove the presence of colitis, then
infliximab
Management of hyperthyroidism
- Hypothyroidism by anti-angiogenic therapy
- Hyperthyroidism: Antithyroid meds, radioactive iodine ablation or surgery.
Management of hyperglycemia
- Dietary modification: Avoidance of high glycemic index food
- Pharmacological intervention: First-Line is metformin, second line other diabetic drugs
