gi alterations gastrointestinal alterations mucositis

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Gastrointestinal

Alterations

Nancy Thompson, RN, MS, AOCNS

Swedish Cancer Institute

GI Alterations

Nausea & Vomiting

Mucositis

Taste Alterations

Anorexia / Cachexia

“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/m2 and cisplatin 100

mg/m2.

She is worried about side effects

because she had a friend who

had a lot of nausea and vomiting.

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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

Delayed: Occurs at least 24 hours after therapy and may persist up

to 6 days

> Cisplatin associated with highest incidence

CINV: Prevalent With Common Regimens Even Today Despite 5-HT3 Use

TAC=docetaxel + doxorubicin + cyclophosphamide;

FOLFOX 6=oxaliplatin + leucovorin + 5-fluorouracil.

Site of Cancer

Breast

Lung

Colorectal

Ovarian

Regimen Vomiting Nausea

TAC 44.5% 80.5%

Carboplatin +

paclitaxel 33.3% 44.3%

FOLFOX 6 42% 67%

Carboplatin +

docetaxel 37% 78%

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

Hesketh PJ. Oncologist. 1999;4:191–196.

Navari RM. J Support Oncol. 2003;1:89–103. NCCN Guidelines. v.3.2008: antiemesis.

Risk Factors for CINV: Patient Characteristics

Female

Age < 50 years

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

Navari RM. J Support Oncol. 2003;1:89–103.

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Classification of Acute Emetogenic Potential of Single Chemotherapeutic Agents

Level 5 Emesis in > 90% of patients

Level 4 Emesis in 60% - 90% of patients



Level 1 Emesis in < 10% of patients

Adapted from Hesketh PJ et al. J Clin Oncol. 1997;15:103-109, ©1997,

with permission from the American Society of Clinical Oncology.

Single Chemotherapeutic Agents With Highest Potential for Acute Emesis

Level Frequency of Emesis Agent

5 > 90%

Carmustine > 250 mg/m2

Cisplatin >= 50 mg/m2

Cyclophosphamide > 1,500 mg/m2

Dacarbazine

Mechlorethamine

Streptozocin

4 60% - 90%

Carboplatin

Carmustine <= 250 mg/m2

Cisplatin < 50 mg/m2

Cyclophosphamide > 750 mg/m2 <= 1,500 mg/m2

Cytarabine > 1 g/m2

Doxorubicin > 60 mg/m2

Methotrexate > 1,000 mg/m2

Procarbazine (oral)



Single Chemotherapeutic Agents With Moderate Potential for Acute Emesis

Level Frequency of Emesis Agent

3 30% - 60%

Cyclophosphamide < 750 mg/m2

Cyclophosphamide (oral)

Doxorubicin 20 – 60 mg/m2

Epirubicin < 90 mg/m2

Idarubicin

Ifosfamide

Irinotecan

Methotrexate 250 – 1,000 mg/m2

Mitoxantrone <15 mg/m2

2 10% - 30%

Capecitabine

Docetaxel

Etoposide

5-FU <1,000 mg/m2

Gemcitabine

Methotrexate >50 <250 mg/m2

Mitomycin

Paclitaxel

Topotecan



Both Peripheral and Central Pathways Play a Role in CINV

1. Tavorath R et al. Drugs. 1996;52:639–648.

2. Grunberg SM, Hesketh PJ. N Engl J Med. 1993;329(24):1790–1796.

Illustration by Kirk Moldoff.

bNeurokinin-1

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Nausea & Vomiting Pharmacologic Management

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

ONS: Putting Evidence into Practice

Serotonin Antagonists

Indications:

> High & moderate to high emetogenic chemotherapy

Common side effects:

> Headache, diarrhea, constipation, fever

Examples:

> ondansetron, granisetron, dolasteron

> Palonosetron (2nd generation)

NK-1 Antagonist

Indications:

> Acute and delayed nausea / vomiting

> Highly emetogenic chemotherapy

Common side effects:

> Diarrhea, hiccups, fatigue

Examples:

> Aprepitant (oral)

> Fosaprepitant (IV)

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CINV Cheat Sheet

Phase of CINV

Acute Events Delayed Events

Mechanism of

Action

Peripheral Pathway Central Pathway

Neurotransmitter Serotonin Substance P

Class of Drug 5HT3 Receptor

Antagonist

NK1 Receptor

Antagonist

Drug Examples Dolasetron,

Granisetron,

Ondansetron,

Palonsetron

Aprepitant

Fosaprepitant


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

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Radiation

Healing Ulceration Signaling &

Amplification

Upregulation

& Message Gen Initiation

Chemotherapy

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.

Pathobiology of Mucositis 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

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

Agents Most Commonly Associated with Mucositis

actinomycin D

amsacrine

bleomycin

cytarabine

daunorubicin

docetaxel

doxorubicin

etoposide

floxuridine

5-fluorouracil

methotrexate

mitoxantrone

plicamycin

thioguanine

vinblastine

vindesine

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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

Sonis et al. (2001); Ruescher, et al. (1998); Elting et al. (2003).

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”

ONS Putting Evidence Into Practice, 2009

Mucositis: Management

Prevention

> Collaborate with a

multidisciplinary team

> Oral care products

> 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


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Magic Mouthwash

Dodd MJ, Dibble SL, Miaskowski C, et al.. (2000).

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

Pro-Self Mouth Aware Program

Magic Mouthwash

Chlorhexidine

Salt/Soda Rinses 2 tsp baking soda

1 tsp salt

1 liter of water

Rinse oral cavity every 2-4 hours or more often as needed.

Make a fresh solution every 24 hours.

Salt and Soda Rinse

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.



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”.

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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

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

Taste Alterations: Consequences

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

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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


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

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

Anorexia: Defined

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

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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.

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) 489 – 495)

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

Andreyev HJN, Eur J Cancer, 1998/34(4) 503-509

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“Malnourished cancer patients do not live as long as their counterparts who

remain well nourished”

Dewys, WD et al. Am J Med, 1980, 69: 491-497

Malnutrition’s Effect on Oncology Patients

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: 491-497

Early Assessment and Intervention is Critical

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

Laboratory Results

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

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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) -160 - 1600 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

Improved nutritional intake and body weight

Reduction in the incidence of anorexia

Improved quality of life

PUTTING EVIDENCE INTO PRACTICE, 2009

Non-pharmacological

Exercise/strength training -

improved lean muscle mass

Refer to cancer rehabilitation or PT

One of the most effective things we

can do!

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Nutritional Alterations

Nausea & Vomiting

Mucositis

Taste Alterations

Anorexia / Cachexia

gi alterations gastrointestinal alterations mucositis

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