Gastrointestinal Alterations

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1 Gastrointestinal Alterations Nancy Thompson, RN, MS, AOCNS Swedish Cancer Institute Nausea & Vomiting Mucositis Taste Alterations Anorexia / Cachexia GI Alterations The Chinese do not draw any distinction between food and medicine. Lin Yutang Case Study: Sarah Hogan A 44 year old female, diagnosed with extensive stage small cell lung cancer. She is told by her oncologist that she will be receiving etoposide 100 mg/m 2 and cisplatin 100 mg/m 2. She is worried about side effects because she had a friend who had a lot of nausea and vomiting. 1

2 Therapy-Related Emesis Patterns Anticipatory: Occurs before or during treatment from associated stimuli; a conditioned response > 25% incidence Acute: Occurs within 24 hours > Incidence determined by agents CINV: Prevalent With Common Regimens Even Today Despite 5-HT3 Use Site of Cancer Breast Lung Regimen Vomiting Nausea TAC 44.5% 80.5% Carboplatin + paclitaxel 33.3% 44.3% Delayed: Occurs at least 24 hours after therapy and may persist up to 6 days > Cisplatin associated with highest incidence Colorectal Ovarian FOLFOX 6 42% 67% Carboplatin + docetaxel 37% 78% TAC=docetaxel + doxorubicin + cyclophosphamide; FOLFOX 6=oxaliplatin + leucovorin + 5-fluorouracil. Risk Factors for CINV: Chemotherapy-Specific Factors Use of moderately or highly emetogenic regimens, such as: > Cisplatin-based regimens > Cyclophosphamide-based regimens (e.g. CHOP) > AC (anthracycline + cyclophosphamide) > Carboplatin-based regimens > ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine) > FOLFOX/FOLFIRI (oxaliplatin + leucovorin + 5FU/irinotecan + leucovorin + 5FU) Short IV infusion time Repeated cycles of chemotherapy Female Age < 50 years Risk Factors for CINV: Patient Characteristics History of low alcohol intake (<1.5 oz/day) History of motion sickness History of morning sickness during pregnancy History of prior CINV Extreme anxiety Other factors > pain, constipation, medications Hesketh PJ. Oncologist. 1999;4: Navari RM. J Support Oncol. 2003;1: NCCN Guidelines. v : antiemesis. Navari RM. J Support Oncol. 2003;1:

Classification of Acute Emetogenic Potential of Single Chemotherapeutic Agents Single Chemotherapeutic Agents With Highest Potential for Acute Emesis Level 5 Emesis in > 90% of patients Level

3 Classification of Acute Emetogenic Potential of Single Chemotherapeutic Agents Single Chemotherapeutic Agents With Highest Potential for Acute Emesis Level 5 Emesis in > 90% of patients Level Frequency of Emesis Agent Level 4 Level 3 Emesis in 60% - 90% of patients Emesis in 30% - 60% of patients 5 > 90% Carmustine > 250 mg/m 2 Cisplatin >= 50 mg/m 2 Cyclophosphamide > 1,500 mg/m 2 Dacarbazine Mechlorethamine Streptozocin Level 2 Level 1 Emesis in 10% - 30% of patients Emesis in < 10% of patients 4 60% - 90% Carboplatin Carmustine <= 250 mg/m 2 Cisplatin < 50 mg/m 2 Cyclophosphamide > 750 mg/m2 <= 1,500 mg/m 2 Cytarabine > 1 g/m 2 Doxorubicin > 60 mg/m 2 Methotrexate > 1,000 mg/m 2 Procarbazine (oral) Adapted from Hesketh PJ et al. J Clin Oncol. 1997;15: , 1997, with permission from the American Society of Clinical Oncology. Adapted from Hesketh PJ et al. J Clin Oncol. 1997;15: , 1997, with permission from the American Society of Clinical Oncology. Single Chemotherapeutic Agents With Moderate Potential for Acute Emesis Both Peripheral and Central Pathways Play a Role in CINV Level Frequency of Emesis Agent 3 30% - 60% 2 10% - 30% Cyclophosphamide < 750 mg/m 2 Cyclophosphamide (oral) Doxorubicin mg/m 2 Epirubicin < 90 mg/m 2 Idarubicin Ifosfamide Irinotecan Methotrexate 250 1,000 mg/m 2 Mitoxantrone <15 mg/m 2 Capecitabine Docetaxel Etoposide 5-FU <1,000 mg/m 2 Gemcitabine Methotrexate >50 <250 mg/m 2 Mitomycin Paclitaxel Topotecan b Neurokinin-1 Adapted from Hesketh PJ et al. J Clin Oncol. 1997;15: , 1997, with permission from the American Society of Clinical Oncology. 1. Tavorath R et al. Drugs. 1996;52: Grunberg SM, Hesketh PJ. N Engl J Med. 1993;329(24): Illustration by Kirk Moldoff. 3

4 Nausea & Vomiting Pharmacologic Management ONS: Putting Evidence into Practice Prevention, prevention, prevention!! Select appropriate antiemetic based on treatment regimen Consider cumulative effects Administer through entire anticipated period of nausea & vomiting Oral and IV antiemetics have equivalent effectiveness Consider other potential causes of emesis Serotonin Antagonists Indications: > High & moderate to high emetogenic chemotherapy Common side effects: > Headache, diarrhea, constipation, fever Examples: > ondansetron, granisetron, dolasteron > Palonosetron (2 nd generation) NK-1 Antagonist Indications: > Acute and delayed nausea / vomiting > Highly emetogenic chemotherapy Common side effects: > Diarrhea, hiccups, fatigue Examples: > Aprepitant (oral) > Fosaprepitant (IV) 4

CINV Cheat Sheet Phase of CINV Acute Events Delayed Events Mechanism of Action Peripheral Pathway Central Pathway Neurotransmitter Serotonin Substance P Class of Drug Drug Examples 5HT

etoposide/cisplatin and comes into the clinic. As part of your nursing assessment, you use a gloved finger and a pen light to carefully look in her mouth.

5 CINV Cheat Sheet Phase of CINV Acute Events Delayed Events Mechanism of Action Peripheral Pathway Central Pathway Neurotransmitter Serotonin Substance P Class of Drug Drug Examples 5HT 3 Receptor Antagonist Dolasetron, Granisetron, Ondansetron, Palonsetron NK 1 Receptor Antagonist Aprepitant Fosaprepitant Case Study: Sarah Hogan Sarah has completed two cycles of her etoposide/cisplatin and comes into the clinic. As part of your nursing assessment, you use a gloved finger and a pen light to carefully look in her mouth. Mucositis Grading Grade Criteria 0 None I Oral soreness, erythema II Oral erythema, ulcers, solid diet tolerated III Oral ulcers, liquid diet only IV Oral alimentation impossible Courtesy of BB Toth, MD Anderson 5

Initiation Radiation Chemotherapy Pathobiology of Mucositis Upregulation & Message Gen Signaling & Amplification Ulceration Healing Risk Factors for Oral Mucositis Patient-related > Age > Gender >

Smoking 0-21 Days Based on: Sonis S. (2003); Sonis S. (2004); Reprinted with permission from The Curry Rockefeller Group, LLC, Cancer Therapy-Induced Oral Mucositis, 2005. Köstler et al. (2001).

6 Initiation Radiation Chemotherapy Pathobiology of Mucositis Upregulation & Message Gen Signaling & Amplification Ulceration Healing Risk Factors for Oral Mucositis Patient-related > Age > Gender > Body Mass Index > Renal Function > Hematologic malignancy > Genetic factors > Previous cancer therapy > Oral health and hygiene > Xerostomia Patient-related > Poorly fitting dental appliances > Smoking 0-21 Days Based on: Sonis S. (2003); Sonis S. (2004); Reprinted with permission from The Curry Rockefeller Group, LLC, Cancer Therapy-Induced Oral Mucositis, Köstler et al. (2001). Risk Factors for Oral Mucositis Patient-related Age Gender Body mass index Renal function Hematologic malignancy Genetic factors Previous cancer therapy Oral health and hygiene Xerostomia Patient-related Poorly fitting dental appliances Smoking actinomycin D amsacrine bleomycin cytarabine daunorubicin docetaxel doxorubicin etoposide Agents Most Commonly Associated with Mucositis floxuridine 5-fluorouracil methotrexate mitoxantrone plicamycin thioguanine vinblastine vindesine 6

7 Impact of Oral Mucositis Clinical Consequences > Dose reduction > Dose/Treatment delay > Morbidity increase fever, increase infection > Mortality 4 fold increase in risk Economic > Increase resource utilization > Increase cost -- $4,500 per day Mucositis: Assessment Subjective: > pain, burning, increased sensitivity, altered taste Objective: > erythema, ulceration, saliva, bleeding, cracked lips, hoarse voice Functional: > Ability to chew, difficulty swallowing or speaking Systematic oral assessment at least daily or at each patient visit Sonis et al. (2001); Ruescher, et al. (1998); Elting et al. (2003). ONS Putting Evidence Into Practice, 2009 Prevention > Collaborate with a multidisciplinary team > Oral care products Mucositis: Management > Patient education (written, verbal, demonstration) > Treat dental problems before cytotoxic therapy > High protein diet > Fluid intake > 1500 ml/day > Cryotherapy for bolus 5-FU Treatment > Oral agents & hygiene > Systemic pain medications > Culture lesions Mucositis: Oral Hygiene Program Routine oral care protocol > Daily oral self-exam, report signs of mucositis > Oral hygiene after each meal and at bedtime, increase to q 2 hours as needed > Floss daily with dental tape > Brush with soft toothbrush, 90 seconds bid > Swish after each meal, at bedtime, at other times with water or mouth rinse (Normal Saline, sodium bicarbonate) Avoid oral irritants including tobacco and alcohol Maintain adequate hydration Use water based moisturizers to protect the lips ONS Putting Evidence Into Practice,

8 Magic Mouthwash Pro-Self Mouth Aware Program Randomized Double-blind, Placebo-controlled study 23 outpatient settings, 142 patients No differences in effectiveness among 3 groups in outcome (pain relief or time to resolution) Salt and soda rinses were least costly Magic Mouthwash Chlorhexidine Salt/Soda Rinses 2 tsp baking soda 1 tsp salt 1 liter of water Salt and Soda Rinse Rinse oral cavity every 2-4 hours or more often as needed. Make a fresh solution every 24 hours. Dodd MJ, Dibble SL, Miaskowski C, et al.. (2000). Cryotherapy for Bolus Mucotoxic Chemotherapy with Short Half Life Bolus 5-fluorouracil (5-FU) & Melphalan Instruct patients to hold ice chips in their mouth starting 5 minutes prior and for 30 minutes after. The effectiveness of this intervention is based on vasoconstriciton of the circulation in the oral cavity and the short half life of these agents. Evidence is lacking to support the benefit with other chemotherapy agents. Do not use in patients receiving oxaliplatin. Case Study: Sarah Hogan Sarah complains that food does not taste the same and that everything tastes like cardboard, especially red meat. She asks you if this is normal. ONS Putting Evidence Into Practice,

9 Taste Alterations: Defined An actual or perceived change in taste sensation or loss of taste > Hypogeusethesia: A decrease in the acuity of the taste sensation > Dysgeusia: An unusual taste perception, perceived as unpleasant > Ageusia: An absence of the taste sensation, mouth blindness True or False? (Hint: Only one is true) 1. Taste changes associated with chemotherapy often resolve once therapy is completed. 2. Approximately one in three cancer patients receiving chemotherapy report taste changes. 3. The most commonly reported intervention to manage metallic taste is to ingest sour candies. 4. Metallic taste changes are often reported with platinum-based chemotherapy regimens. Taste Alterations: Causes Taste Alterations: Consequences Disease related > Invasion of the tumor > Oral infections > Excretion of amino acid-like substances from the tumor cells Treatment related > Specific surgical sites > Radiation > Chemotherapy: Lowered threshold for bitter taste Increased threshold for sweet, sour and salty taste Aversion to meats Metallic taste Anorexia/poor appetite Decreased oral intake Reduced energy levels Poor quality of life Altered or perverted sense of taste for certain foods * Can persist for hours, weeks or months after treatment 9

10 Taste Alterations: Management Experiment with spices and flavorings Use the aroma of foods to stimulate taste Encourage oral hygiene before and after meals Add increased sweeteners Substitute other sources of protein (non-meat) Marinate meats in sweet marinades Avoid the sight and smell of foods causing unpleasantness Avoid alcohol, commercial mouthwashes, smoking Consume hard candies and / or chew gum to change taste before meals and before chemotherapy treatment to reduce metallic taste Use plastic eating utensils to manage the metallic taste Refer to dietitians for nutritional counseling Assess for weight loss Case Study: Sarah Hogan Before beginning her 4th cycle of etoposide/cisplatin, Sarah comes in to the clinic for her assessment. You notice that she has lost 15 pounds since her baseline weight. She tells you that she has no appetite. Common Nutritional Challenges Anorexia: Defined Anorexia Malnutrition Weight Loss Muscle mass loss Cachexia At diagnosis: 50% of patients present with nutritional issues Malnutrition is the most common secondary diagnosis to cancer Involuntary loss of appetite accompanied by decreased food intake Often accompanied by weight loss May be insidious and may only be obvious by weight loss Can lead to cachexia Often is not treated or diagnosed 10

11 Malnutrition: Defined A state of nutrition in which a deficiency, excess or imbalance of energy, protein, and other nutrients causes measurable adverse effects on body function and clinical outcome. Anorexia and Malnutrition: Causes Physiologic: Concurrent symptoms > Nausea/vomiting > Early satiety > Pain > Dysphagia > Mucosisits > Ascites > Fatigue Structural problems > Abdominal tumors > Surgical and dental changes Medications > Narcotics, iron, antibiotics Psychological > Anxiety, depression > Loss of pleasure associated with food Social factors > Companionship > Eating environment > Issues associated with food preparation Cachexia: Defined A multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment 1. Pre-cachexia - Weight loss of less than 5%. Anorexia and metabolic change 2. Cachexia - Weight loss of more than 5% or BMI less than 20 and weight loss greater than 2% or sarcopenia and weight loss more than 2%. Reduced food intake and systemic inflammation. Patients with weight loss have worse outcomes Chemotherapy dose reductions Increase dose limiting toxicity Decreased treatment response Decreased quality of life and performance status Shorter survival 3. Refractory Cachexia Variable degree of cachexia. Cancer disease both pro-catabolic and not responsive to anticancer treatment. Low performance status. Less than 3 months expected survival. Fearon K., Lancet Oncol. 2011; 12(5) ) Andreyev HJN, Eur J Cancer, 1998/34(4)

Malnutrition s Effect on Oncology Patients Malnourished cancer patients do not live as long as their counterparts who remain well nourished Just a small loss of weight may be a sign of a nutritional

12 Malnutrition s Effect on Oncology Patients Malnourished cancer patients do not live as long as their counterparts who remain well nourished Just a small loss of weight may be a sign of a nutritional decline that leads to: > Treatment Delays > Complications > More frequent hospitalizations > Reduced key outcomes such as quality of life Dewys, WD et al. Am J Med, 1980, 69: Dewys, WD et al. Am J Med, 1980, 69: Early Assessment and Intervention is Critical Laboratory Results Dietary factors > Diet history > Ability to purchase & prepare food > Food preferences / aversions > Calorie count / food diary > Educational needs Physical Exam > Weight loss > Functional status Laboratory Data > Pre-albumin, albumin, transferrin Serum albumin > Measures visceral protein stores > Less than 3.5 g/dl shows recent protein depletion Serum prealbumin > Less than 15 mg/dl > Indicates protein depletion Serum transferrin > Less than 200 mg/dl > Reflects a decrease in the body s ability to make serum proteins 12

13 Anorexia / Cachexia: Management Treat the tumor (keep patients on treatment!) Early and regular assessment (weight % and time) Early intervention prior to a crisis Manage anorexia causes (N & V, Mucositis, pain) Consider appetite stimulants > Corticosteroids, progestins Consider nutritional supplements with Revigor > Ensure clinical Strength or Juven Dietary Counseling Non-pharmacological > small, frequent meals, oral hygiene, exercise, high calorie, high protein foods & supplements Recommended Appetite Stimulants Corticosteroids: Prednisolone, Dexamethasone > Improve appetite, food intake, sense of well-being and performance status > Most effective type, dose or route not established > Benefit is significant yet short in duration > Long term use is associated with significant toxicities Megestrol acetate (Megace) mg daily > Most widely studied > Dose related benefit on appetite, caloric intake and body weight and sensation of well-being. > Not to be used in patients at risk for thromboembolic disease, heart disease or serious fluid retention Individualized Dietary Counseling Non-pharmacological Improved nutritional intake and body weight Reduction in the incidence of anorexia Improved quality of life Exercise/strength training - improved lean muscle mass Refer to cancer rehabilitation or PT One of the most effective things we can do! PUTTING EVIDENCE INTO PRACTICE,

14 Nutritional Alterations Nausea & Vomiting Mucositis Taste Alterations Anorexia / Cachexia 14

Symptom Management of Gastrointestinal Alterations

Symptom Management of Gastrointestinal Alterations Parisa Tsutsumi RN, BSN, OCN, BMTCN University of Washington Medical Center Nausea and Vomiting Mucositis Taste Alterations Gastrointestinal Alterations