Nutritional Complications of Anti-cancer Therapy (Week 6 Lecture 2)

Question 1

How is nutritional compromise commonly observed in cancer patients?

Answer 1

• weight loss
• anorexia
• malabsorption
• maldistribution of fat and lean body masses, including liver and muscles

Question 2

What results in nutritional compromise?

Answer 2

• cancer
• malabsorption
• surgery
• radiation
• systemic therapy

Question 3

How does cancer result in nutritional compromise?

Answer 3

• Production of inflammatory mediators leading to catabolism of muscles and fat.
• Decrease in intake due to dysphagia and early satiety.

Question 4

How does systemic therapy result in nutritional compromise?

Answer 4

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.

Question 5

What is indirect nutritional complications?

Answer 5

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

Question 6

Grading of toxicity

Answer 6

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.

Question 7

Describe the complication of dysgeusia?

Answer 7

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

Question 8

Grading for dysgeusia

Answer 8

• 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

Question 9

Describe the nutritional complications of nausea and vomiting

Answer 9

• 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

Question 10

Grading for nausea

Answer 10

Question 11

Grading for vomiting

Answer 11

Question 12

Nutritional complications of anorexia/ early satiety

Answer 12

Feeling full in the stomach earlier than expected, leading to total reduction of food intake or preferential food intake.

Question 13

Causes of anorexia/ early satiety other than chemotherapy

Answer 13

• Obstruction of gastric outlet or duodenum
• Inflammatory mediators of cancer
• Delay in gastric emptying.

Question 14

Grading for anorexia

Answer 14

Question 15

What is mucositis?

Answer 15

Inflammation of the mucous membrane (sores)

Question 16

Where is mucositis observed?

Answer 16

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)

Question 17

grading for oral mucositis

Answer 17

Question 18

Describe esophagitis

Answer 18

inflammation of esophagus

Question 19

What results in esophagitis?

Answer 19

• 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.

Question 20

Grading for esophagitis

Answer 20

Question 21

What results in malabsorption?

Answer 21

• Resection of part of bowels
• Radiation
• Chemotherapy

Question 22

resection of bowel parts causing malabsorption

Answer 22

• 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.

Question 23

Radiation causing malabsorption

Answer 23

Mucosal damage leading to a combination of malabsorption and secretory diarrhea.

Question 24

Chemotherapy causing malabsorption

Answer 24

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.

Question 25

Grading for malabsorption

Answer 25

Question 26

What results in diarrhea?

Answer 26

* **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

Question 27

Grading for diarrhea

Answer 27

Question 28

What may result in hyperlipidemia?

Answer 28

* 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.

Question 29

Grading for hyperlipidemia

Answer 29

Question 30

What results in hypothyroidism?

Answer 30

* 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)

Question 31

Grading for hypothyroidism

Answer 31

Question 32

What results in hyperglycemia?

Answer 32

* Hyperglycemia due to autoimmune mechanism: destruction of the Islet cells by auto-antibody * Altered glucose metabolism

Question 33

What might cause altered glucose metabolism?

Answer 33

* 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.

Question 34

Grading for hyperglycemia

Answer 34

Question 35

What results in fatty liver?

Answer 35

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.

Question 36

general medical management of nutritional complications

Answer 36

Education: * Patients and family * Nursing and dietitians * OURSELVES. Monitoring: * General dietary questions * Physical examination * Laboratory investigations: Ca, glucose, TSH, albumin * Scans for sarcopenia.

Question 37

Management of dysgeusia

Answer 37

* 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.

Question 38

Management of nausea/ vomiting

Answer 38

* medication for moderate/high * medication for low day 1 pre-chemo

Question 39

Management of mucositis & esophagitis

Answer 39

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

Question 40

Management of anorexia

Answer 40

* nutritional supplementation: protein intake, EN vs. PN * Appetite stimulants: steroid, cannabinoid, anti-depressant

Question 41

Management for hyperlipidemia

Answer 41

* Diet modification as advised by the Canadian Heart Association. * Pharmacological intervention: HMG co-A inhibitors * Exercise.

Question 42

Management of diarrhea

Answer 42

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

Question 43

Management of hyperthyroidism

Answer 43

* Hypothyroidism by anti-angiogenic therapy * Hyperthyroidism: Antithyroid meds, radioactive iodine ablation or surgery.

Question 44

Management of hyperglycemia

Answer 44

* Dietary modification: Avoidance of high glycemic index food * Pharmacological intervention: First-Line is metformin, second line other diabetic drugs