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Hematologic Function

Lenise Taylor, MN, RN, AOCNS, BMTCN

Symptom Management: 22%

A. Etiology and patterns of symptoms (acute, chronic, late) B. Toxicity and grading scales C. Anatomical and surgical alterations D. Complementary and integrative modalities (e.g. massage, acupuncture, herbal

supplements) E. Alterations in:

1. Hematologic function 8. Cardiovascular function 2. Immune function 9. Neurological function 3. Gastrointestinal function 10. Musculoskeletal function 4. Nutrition status 11. Comfort (e.g. pain) 5. Integumentary function 6. Genitourinary function 7. Respiratory function

Myelosuppression • Definition:

– Reduction in production & maturation of all blood cell lines

– Resulting in:

• Neutropenia and leukopenia,

• Thrombocytopenia

• Anemia

• One of most common & potentially life-threatening clinical complications experienced by patients with cancer

Shelton, B. In Holmes Gobel, B., et al eds. Advanced Oncology Nursing Certification: Review & Resource Manual. 2009: 405-442.

Platelets 7-8 Days

Neutrophil 7-12 Hours

Eosinophil 3-8 Hours

Basophil/mast cell 7-12 Hours

Monocyte/macrophage 3 Days

B Lymphocyte Type depend

T Lymphocyte Type depend

Erythrocyte 120 Days

Blood Cell Life Span in Blood

CIRCULATING BLOOD CELLS

LIFE SPAN

Neutropenia

Decreased number of circulating neutrophils

Associated with increased risk of potentially life-threatening infection

Neutrophils 1st line of defense against bacterial infection (localize & neutralize bacteria)

Normal rage (neutrophils)

2,500 to 6,000 cells/mm3

50% to 60% of total number of WBC’s

More than 50% of patients with neutropenia can be expected to develop infection.

https://www.ons.org/practice-resources/pep/prevention-infection, accessed June 10, 2014

White Blood Cell (WBC) Count Differential

WBC Type Relative Value

Absolute Value uL (mm3)

Neutrophils (total) 50-70% 2,500 – 7,000

segmented (polys) 50-65% 2,500 – 6,500

bands 0-5% 0 – 500

Eosinophils 1-3% 100 - 300

Basophils 0.4-1.0% 40-100

Monocytes 4-6% 200-600

Lymphocytes 25-35% 1,700-3,500

Kee, J.L. Laborator & Diagnositc Tests with Nursing Implications. 1999.

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Neutropenia Risk Factors

■ Pre-existing neutropenia – Comorbidities, previous treatment

■ Myelosuppressive chemotherapy

■ Bone marrow involvement

■ Immune system degeneration

■ Hepatic and renal dysfunction

■ Malnutrition

■ Combined modality treatment

Assessing Neutrophils: The Absolute Neutrophil Count (ANC)

ANC = Total WBC X % of neutrophils (segs + bands)

Example:

WBC = 2,500/mm3

Segmented neutrophils = 35%

Band neutrophils = 10%

ANC = 2,500 X (.35 + .10) =

ANC = 2,500 X .45 = 1,125/mm3

Absolute Neutrophil Count Calculation

WBC = 3,000/mm3

• Segmented neutrophils = 20%

• Band neutrophils = 5%

• Eosinophils = 3%

• Basophils = 1%

• Lymphocytes = 71%

What is the ANC?

ANC = 3,000/mm3 X .25 = 750

The ANC Predicts the Risk for Infection

Absolute Neutrophil Count

Grade

Risk of Infection

Within normal limits 0 No Risk

> 1,500 to <2,000 1 No significant risk

> 1,000 to < 1,500 2 Minimal risk

> 500 to <1,000 3 Moderate risk

< 500 4 Severe risk

Camp-Sorrell, D. In Itano, J. & Taoka, K. eds. Core Curriculum for Oncology Nursing, 4th Ed. 2005: 259-274.

Potential Consequences of Neutropenia

• Delay in administering treatment on time or dose delay; dose reductions

• Infection

• Sepsis and septic shock

• Death

Camp-Sorrell, D. In Itano, J. & Taoka, K. eds. Core Curriculum for Oncology Nursing, 4th Ed. 2005: 259-274

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Preventing Infection

• Frequent hand washing

• Daily bathing

• Frequent mouth care

• Limit invasive procedures

– Rectal temps, catheters, etc.

• Inspect IV sites

• Visitor hygiene

Camp-Sorrell, D. In Itano, J. & Taoka, K. eds. Core Curriculum for Oncology Nursing, 4th Ed. 2005: 259-274.

Nursing Management: Continual Assessment for Infection

• Signs of infection MAY NOT be present

• Redness, inflammation, and drainage may be minimal or absent

Shelton, B.K. (2009). In Gobel, B.H. et al (eds.). Advanced Oncology Nursing Certification: Review and Resource

Manual, ONS, pgs. 405-442.

Nursing Assessment: Every 4 hours (inpatient)

& at each clinic visit (outpatient)

■ Vital signs every 4 hours ■ Level of consciousness ■ Intake and output ■ Respiratory status & auscultate

lungs ■ Presence, character and amount

of sputum, cough ■ Skin integrity, especially at

catheter or tube insertion sites, incisions or perirectal area

■ Oral cavity for plaque, thrush, ulcers, redness, dryness

■ Character, amount and frequency of stool

■ Character, amount and frequency of urine

■ Assess peri-anal area daily for signs of infection for patients who are severely neutropenic

■ Monitor CBC and other labs for changes, if ordered

■ Assess central venous access site for signs of infection

■ Consider MD order for GCSF

Putting Evidence Into Practice (PEP) Resources

■ Green = GO! – Recommended for Practice – Likely to Be Effective – Evidence supports the consideration of

these interventions in practice ■ Yellow = CAUTION! – Benefits Balanced with Harm – Effectiveness Not Established – Not sufficient evidence to say whether

these interventions are effective or not ■ Red = STOP! – Effectiveness Unlikely – Not Recommended for Practice – Evidence indicates these interventions

are ineffective or harmful

https://www.ons.org/practice-resources/pep, accessed June 10, 2014

Prevention of Infection (General): Recommended for Practice

• Hand Hygiene with alcohol sanitizer • Contact precautions for resistant

organisms • Colony-stimulating factors

– Chemotherapy with > 20% risk of febrile neutropenia or at risk patients

• Influenza vaccine annually for all cancer patients – 2 weeks prior to or 3 months

after immunosuppressive therapy

• Catheter care bundle

https://www.ons.org/practice-resources/pep/prevention-infection/prevention-infection-general, accessed June 10, 2014.

Medical Management: Myeloid Growth Factors

• Filgrastim (Neupogen) or Tbo-Filgrastim (Granix) – Daily dose of 5 mcg/kg until post-nadir ANC recovery

to normal or near-normal levels

– Start 24-72 h after completion of chemotherapy and treat through post-nadir recovery

– Administration of growth factor on same day of therapy is not recommended

• Pegfilgrastim (Neulasta) – One dose of 6 mg per cycle of treatment

– Start 24-72 h after completion of chemotherapy

NCCN (2009). Myeloid Growth Factors: Practice Guidelines. Accessed at www.nccn.org, 08/24/09

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Recommended for Practice (General)

■ Pneumococcal vaccine for all cancer patients

– At least 2 wks prior to chemo, if possible

■ Antibiotic prophylaxis with flouroquinolones for patients at high risk for infection

– Hematologic malignancies – BMT recipients – Expected neutropenia > 7 days ■ Antifungal & antiviral prophylaxis in high-

risk patients – Acute leukemia, MDS – BMT, patients with GVHD

https://www.ons.org/practice-resources/pep/prevention-infection/prevention-infection-general, accessed June 10, 2014.

Likely to Be Effective (General)

• Preconstruction planning • Chlorhexidine impregnated washcloths

– chlorhexidine bath • Antibiotic impregnated IV catheters in

adults (short-term catheters only) • Antibiotic abdominal lavage in

colorectal surgery

https://www.ons.org/practice-resources/pep/prevention-infection/prevention-infection-general, accessed June 10, 2014.

Benefits Balanced with Harm (General)

• Intravenous Immunoglobulin (IVIG)

https://www.ons.org/practice-resources/pep/prevention-infection/prevention-infection-general, accessed June 10, 2014.

Effectiveness Not Established (General) ■ Chlorhexidine sponge dressing

■ Protective isolation

■ Staff training

■ Cranberry juice

■ Antibiotic IV catheter lock solutions

■ Antibiotic coated sutures

Effectiveness Unlikely

• Extended post-operative antibiotics

• Restriction of fresh fruits and vegetables

https://www.ons.org/practice-resources/pep/prevention-infection/prevention-infection-general, accessed June 10, 2014.

Not Recommended For Practice

■ Live attenuated vaccines

– Flumist (intranasal attenuated influenza vaccine)

– Varicella (chicken pox) vaccine, oral polio vaccine, & MMR vaccine

■ Implantable gentamycin sponge

Detecting Signs of Infection in Patients with Neutropenia

• Neutropenia: the often silent disorder

• ONLY sign of an infection may be FEVER:

– Take temperature every 4 hours (inpatient)

– Instruct patient to take temperature QD or BID (home)

– Report temperature > 1010F (38.00C) or 100.50 F (37.50 ) for > 1 hr

– Tachycardia & tachypnea alone, may be developing sepsis

– Hypotension with above indicates severe sepsis

Shelton, B.K. (2009). In Gobel, B.H. et al (eds.). Advanced Oncology Nursing Certification: Review and Resource

Manual, ONS, pgs. 405-442.

Educate Patients & Caregivers to Recognize & Minimize Infection

• List measures to prevent infection

– Managing environment, hygiene, diet, activity

• Identify signs & symptoms of infection

• Emphasize when to report

– Fever or other signs/symptoms of infection

– Be specific about whom and when to call

• Give specific oral & written instructions

Camp-Sorrell, D. In Itano, J. & Taoka, K. eds. Core Curriculum for Oncology Nursing, 4th Ed. 2005: 259-274.

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Febrile Neutropenia

• ALWAYS A MEDICAL EMERGENCY

• Left untreated, may be fatal

• Sepsis is lethal in 47% of infected patients with neutrophil count <1000

Giamarellou, H. & Antoniadou, A. (2001). Infections complications of febrile leukopenia. Infectious Disease Clinics of

North America, 15: 457-482.

Febrile Neutropenia: Definition

• Febrile neutropenia

– Single temperature > 38.30C orally or >38.00C over 1 hr

• Neutropenia

– < 500 neutrophils/mcL or <1,000 neutrophils/mcL and a predicted decline to <500/mcL over the next 48 hrs

NCCN (2009). Myeloid Growth Factors: Practice Guidelines. Accessed at www.nccn.org, 08/24/09

Assessing/Managing Neutropenic Patients with Fever

• Obtain blood cultures • Culture suspected sites of infection

– Urine, sputum, stool, IV catheter sites, wounds

• Chest x-ray • Immediate institution of broad

spectrum antibiotics • Admission to hospital

(ANC<1000)

Thrombocytopenia

• Decrease in circulation platelets below 100,000/mm3

– Normal platelet count 150,000 – 400,000/mm3

– Life span of platelets – 8 to 10 days

Platelet Count Grade Risk of Bleeding

Within normal limits 0 No Risk

< LLN – 75,000/mm3 1 No significant risk

<75,000 – 50,000/mm3 2 Minimal risk

< 50,000 – 25,000/mm3 3 Moderate risk

< 25,000/mm3 4 Severe risk

Camp-Sorrell, D. In Itano, J. & Taoka, K. eds. Core Curriculum for Oncology Nursing, 4th Ed. 2005: 259-274.

National Cancer Institute Cancer Therapy Evaluation Program (NCI CTEP), 2006.

Clinical Consequences of Thrombocytopenia

• Bleeding – Internal or External

• Refractory to platelet transfusions

Recommended for Practice

• Platelet thresholds: keep at – 10,000: majority of patients – 20,000

• minor procedures • bladder tumors, necrotic

tumors, or highly vascular tumors likely to bleed

– 40,000 – 50,000: patients undergoing invasive procedures

• Platelet transfusions – Active bleeding with

thrombocytopenia • Mesna for prevention of hemorrhagic

cystitis

http://www2.ons.org/Research/PEP/bleeding, accessed June 10, 2014

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Effectiveness Not Established

• Platelet growth factors

• Recombinant Interleukin-11 (Neumega)

• Interventions to prevent or attenuate menstrual bleeding

• Oral contraceptives, progesterone, etc.

• Desmopressin (DDAVP)

• Epsilon amino-caproic acid (EAC)

• Recombinant activated factor VI (rFVIIA)

• Recombinant epidermal growth hormone (rhEGF) for urothelial protection

• Endoscopic procedures to attentuate bleeding

• Ultrasonic-activated surgical instruments for endovascular embolization procedures

http://www2.ons.org/Research/PEP/bleeding, accessed June 10, 2014

Nursing Assessment: Every 4 hours (inpatient)

& at each clinic visit (outpatient)

■ Bruises, petechiae or bleeding from orifices

■ Monitor for occult or frank blood in urine, stool, or emesis

■ Hypotension or tachycardia

■ Monitor platelet count, coagulation tests (if suspect Disseminated Intravascular Coagulation)

■ Monitor hemoglobin/hematocrit

■ Monitor pad count during menses

■ Monitor for changes in level of consciousness

■ Monitor fall risk, re-evaluate and re-score as necessary

■ Assess safety of patient environment

Reportable Concerns

• Platelet count

– <50,000/mm3 or

– new event < than 15,000 /mm3

• ↓ BP and ↑ pulse rate

• Occult positive results from stools, emesis or urine

• Spontaneous bleeding (increased risk when platelets are < 15,000/mm3)

• Alterations in neurologic signs

• Any new or severe pain, sudden onset of pain, or a sharp exacerbation of existing pain

Safety Concerns

Platelets < 50,000/mm3

• No IM injections

• No rectal temperatures

• No suppositories (unless cleared by MD)

• Minimize invasive procedures

• Avoid medications that have potential to cause bleeding (i.e. anti-inflammatories, aspirin)

• No straight edge razors

• Consider head CT if head strike with fall or new neuro symptoms

Patient Education

■ Report signs of bleeding

■ Preventative and management measures

Anemia

■ A term that indicates a low red cell count

and a below normal hemoglobin or hematocrit level.

Hemoglobin (g/dl)

Grade

Severity of Anemia

Within normal limits 0 Normal

10 - normal 1 Mild

8 - <10 2 Moderate

6.5 - < 8 3 Severe

< 6.5 4 Life threatening

Adapted from the Common Toxicity Criteria for adverse events. Available at:

http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev4.pdf

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Anemia Pathophysiology

■ Question: What is the lifespan of a red blood cell?

Anemia Risk Factors

• Chemotherapy

• Biotherapy

• Bone marrow involvement

• Radiation therapy

• Bleeding

• Age

• Nutritional deficit

• Abnormal metabolism

• Medications

Nursing Assessment: Every 8 hours (inpatient)

& at each clinic visit (outpatient)

• Fatigue

• Hypotension

• Tinnitus

• Headache

• Prolonged capillary refill (monitor hemoglobin)

• Dyspnea

• Palpitation

• Weakness

• Vertigo

• Consider MD order for erythropoietic-stimulating agent to increase RBC (i.e., erythropoietin)

Anemia Management

■ Recognize symptoms

■ Identify and manage underlying cause

– Administer iron supplements

– Consider transfusions

– Consider recombinant erythropoietin*

– Symptom management ■ Energy conservation

■ Oxygen therapy

■ Monitor labs (CBC, iron, total iron binding capacity, transferrin saturation)

Case Study • D.S. comes to the clinic for his 4th course of R-CHOP • Current lab values

• ANC: 950 • H/H: 10.2/30.7 • Platelets: 93,000

• Patient reports increasing fatigue, no fevers, no obvious bleeding

• Patient is anxious to get his treatment completed so he can get back to work full-time.

• What patient education is needed?

Case Study ■ What would the nurse educate the patient about

at this point?

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Fatigue

“Cancer-related fatigue is a distressing, persistent, subjective sense of physical, emotional, or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning”

NCCN, 2008

Cancer-Related Fatigue

• Sleep disorders

• Emotional distress

– Anxiety

– Depression

• Anemia

• Malnutrition

• Decreased activity

• Pain

Based on “Pharmacologic Treatment of Cancer-Related Fatigue” by J. Carroll et. al. 2007, Oncologist, 12(Supp. 1) p. 44. Retrieved December 11, 2007, from http://wwwtheOncologist.com.

Cancer Related Fatigue

Non-cancer comorbidities

• Cardiac dysfunction

• Hepatic dysfunction

• Hypothyroidism

• Infection

• Neurologic dysfunction

• Pulmonary dysfunction

Based on “Pharmacologic Treatment of Cancer-Related Fatigue” by J. Carroll et. al. 2007, Oncologist, 12(Supp. 1), p. 44. Retrieved December 11, 2007, from http://wwwtheOncologist.com.

Fatigue Assessment

■ Fatigue scale (age appropriate)

■ Disease status (recurrent or progression)

■ Current medications

■ Review of systems

■ Onset, pattern, and duration

■ Nutritional and metabolic evaluation

■ Activity level

■ Associated or alleviating factors

Fatigue Collaborative Management

• General

– Energy conservation

– Delegate

– Energy-saving devices

– Patient and family education

• Non-pharmacologic

– Exercise

– Complementary therapies

• Pharmacologic

– Erythropoiesis-stimulating agents

– Antidepressants

– Psychostimulants

– Glucocorticoids

– Supplements

– Complementary therapies

Fatigue Recommended for Practice

• Exercise – Exercise interventions in patients with

cancer have been provided as

• Home-based programs

• Patient self-managed programs

• Supervised and unsupervised individual or group exercise sessions

• Varying duration and frequency and can include combinations of aerobic and resistance types of activities.

https://www.ons.org/intervention/exercise-3, accessed June 10, 2014.

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Fatigue: Likely to Be Effective

■ Abiraterone Acetate ■ Cognitive behavioral

interventions/approach for sleep ■ Energy conservation and activity

management ■ Ginseng ■ Management of concurrent symptoms ■ Massage ■ Mindfulness-based stress reduction ■ Modafinil ■ Psychoeducational interventions ■ Yoga

https://www.ons.org/practice-resources/pep/fatigue, accessed June 10, 2014.

Fatigue Benefits Balanced with Harm

• Erythropoiesis stimulating factors (ESA’s)

https://www.ons.org/practice-resources/pep/fatigue, accessed June 10, 2014.

■ Acupressure/puncture/stimulation

■ Animal-assisted therapy

■ Art making/art therapy

■ Body-mind-spirit therapy

■ Bupropion

■ Co enzyme Q 10

■ Cognitive Training – group

Effectiveness Not Established (Partial List)

■ Cranial Stimulation

■ Dexamphetamine

■ Environmental interventions

■ Expressive writing

■ Meditation

■ Methylphenidate

Risk factors for infection include:

a. Altered mucosal barriers

b. Trimming fingernails and toenails

c. Daily bathing

d. Strict handwashing

The normal life span of platelets is:

a. 1 to 3 days

b. 4 to 5 days

c. 6 to 7 days

d. 8 to 10 days

How is an ANC calculated?

a. % neutrophils (segs + bands) divided by total WBC

b. Total WBC divided by % neutrophils (segs + bands)

c. % neutrophils (segs + bands) multiplied by WBC

d. Actual number of neutrophils (segs + bands) multiplied by WBC

Radiation to which of the following areas can result in myelosuppression?

a. Iliac crests, vertebrae, ribs, skull, sternum, and long bones

b. Tibia, ribs, skull, & sternum

c. Ulna, sternum, & vertebrae

d. Skull, ribs, patella, and metacarpals

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A patient who completed treatment for malignant melanoma one year ago complains of still being tired. The nurse anticipates an

order for:

a. Darbopoetin

b. Methylphenidate

c. Lorazepam

d. pegfilgrastim

Gastrointestinal Function & Nutritional Alterations

GI Function & Nutritional Alterations

• Diarrhea

• Constipation

• Nausea & Vomiting

• Mucositis

• Taste Alterations

• Anorexia / Cachexia

GI Symptoms - Why does it matter?

• GI toxicity can result in dose reductions and treatment delays

• Quality of Life Issues

• Lead to a cascade of other symptoms

Diarrhea

Greater than 200 g/day of fecal output with a volume of

300 ml that is 70 – 90% water and more than three

stools per day.

Types

• Acute - 24 – 48 hours of contact with an agent and resolves within 7 – 14 days or earlier with intervention

• Chronic diarrhea - late onset, lasts for 2 – 3 weeks, occurs as the result of an unidentified agent or as the result of tissue injury related to a treatment modality that interferes with normal bowel function.

• Radiation induced - typically occurs within 2 weeks of beginning radiation therapy

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Types

■ Osmotic – large volume that resolved with fasting or elimination of the provoking agent

■ Secretory – large volume that persists despite fasting

■ Exudative – inflammation, necrosis and sloughing of the colonic mucosa. Occurs more than 6 times per day of variable volume

■ Chemotherapy induced - frequent, watery to semisoild stools with abdominal pain, cramping & fecal incontinence

■ Radiation induced

■ Dysmotility associated - uncoordinated control of intestinal propulsions with rapid transit of stool . Small frequent semisolid stools of variable amounts

Diarrhea: Assessment

Adverse Event 1 2 3 4 5

Diarrhea Increase of < 4

stools per day

over baseline;

mild increase

in ostomy

output

compared to

baseline

Increase of 4-

6 stools per

day over

baseline; IV

fluids

indicated < 24

hrs; moderate

increase in

ostomy output

compared to

baseline; not

interfering

with ADL

Increase of >7

stools per day

over baseline;

incontinence; IV

fluids > 24 hrs;

hospitalization;

severe increase

in ostomy output

compared to

baseline;

interfering with

ADL

Life-threatening

consequences

(e.g.,

hemodynamic

collapse)

Death

From Common Terminology Criteria for Adverse Events (Version 3.0), by the National Cancer Institute Cancer Therapy Evaluation Program,

2006. Retrieved March 31, 2009, from http://ctep.cancer.gov/forms/CTCAEv3.pdf

Diarrhea: Risk Factors

• Radiation therapy

• 5-FU + high dose leucovorin or weekly 5FU

• Immunosuppression

• Bowel surgery

• Neutropenic sepsis

• C. difficile, candida

• GVHD

• Dietary causes

• Inflammatory conditions

• Malabsorption

• Anxiety and stress

Diarrhea: High-Risk Agents

• Chemotherapy:

• Irinotecan

• 5-FU

• Paclitaxel

• Dactinomycin

• Dacarbazine

• Capecitabine

• Biotherapy:

• IL-2

• Interferons

• Targeted agents

• MoAbs

• Imatinib mesylate

• Dasatinib

• Erlotinib

• Bortezomib

• Lapatinib

• Gefitinib

• Sunitinib malate

• Temsirolimus

• Revlamid and thalidomide

• Zolinza

Diarrhea: Clinical Manifestations

• Dehydration (especially children) • Life-threatening electrolyte imbalances • Cardiovascular compromise, orthostasis • Impaired immune function • Skin breakdown • Reduced absorption of oral meds • Pain • Anxiety • Exhaustion/decreased quality of life

Diarrhea: Management

• Monitor stool number, amount, consistency

• Consider other medications that could contribute

• Consider diet and herbal supplements

• Replace fluid and electrolytes

• BRAT diet

Administer antidiarrheal medication Diphenoxylate Loperamide Octreotide Anticholinergics

Increase clear fluid intake (with electrolytes)

Skin care in the peri-rectal area, especially if neutropenic

Early and aggressive patient education

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ONS PEP Resource: Chemotherapy-Induced Diarrhea

■ Likely to be Effective – Octreotide Treatment ■ Benefits Balanced with Harm – Amifostine – Neomycin ■ Effectiveness Not Established – AG1004 -Probiotics – Budesonide -Prophylactic Octreotide – Charcoal – Glutamine – Levofloxacin and Cholestyramine – Oral Alkalinization

ONS PEP Resource: Radiation-Induced Diarrhea

■ Likely to be Effective – Psyllium Fiber ■ Effectiveness Not Established – Dietary Restrictions (fiber & lactulose) – Elemental diet – Glutamine – Probiotics – Vitamin E & C ■ Effectiveness Unlikely – Octreotide -Pentosan Polysulfate ■ Not Recommended for Practice – Sucralfate

Constipation

(Reprinted with permission from Lenz Marketing, Decatur, GA)

Causes: •Presenting symptom of cancer •Side effect of treatment •Result of tumor progression •Unrelated to cancer or treatment

Affects 40% - 70% of cancer patients

Constipation: Assessment

• Patterns of elimination • Dietary intake • Activity level • Abdominal pain or cramping • Characteristics of last BM • Current medications • Laboratory values • Abdominal/rectal exam • Radiographic studies

Agents that decrease motility of the large intestine

• Vinca alkaloids

• Agents that increase nausea and vomiting (thereby decreasing oral intake)

• Opioids

• Anti-depressants

• Iron supplements

• Diuretics

• OTC analgesics (Tylenol, NSAIDs)

• Incidence

– Vinblastine: 20-35%

– Vinorelbine: 35%

– Thalidomide: 55%

– Bortezomib: 41%

Constipation: Clinical Consequences

• Abdominal or rectal discomfort

• Nausea/vomiting

• Anorexia

• Impaction

• Ileus

• Anal fissures

• Hemorrhoids

• Ruptured bowel and life-threatening sepsis

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Constipation: Laxative Options

• Bulk forming

• Lubricants and emollients

• Saline laxatives

• Osmotic laxatives

• Polyethylene glycol (with or without electrolytes)

■ Detergent laxatives

■ Stimulant laxatives

■ Suppositories

■ Prokinetic agents

■ Methylnaltrexone

■ Combination laxative-stool softener prophylactically for patients receiving vinca alkaloids.

Constipation: Non-pharmacologic

interventions

• Increase physical activity or passive exercise

• Maintain usual bowel habits during hospitalization

• Increase fluid and fiber intake • Do not perform rectal exams, use

suppositories or enemas if myelosuppressed

• Consider rotating opioids

ONS PEP Resource: Constipation

■ Recommended for Practice – Methylnaltrexone – Oxycodone/Naloxone – Transdermal Fentanyl

■ Likely to Be Effective – Alvimopan – Amidotrizoate – Polyethylene Gylcol (PEG) – Prophylactic laxatives for patients on opioids – Senna and Docusate

ONS PEP Resource: Constipation

■ Effectiveness Not Established

– Baker’s Yeast -Massage/Aromatherapy

– Biofeedback -Naloxone

– Biscodyl -Opioid Switching

– Colchicine -Probiotics

– Lactulose -Sorbitol

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

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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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.

NCCN Guidelines. v.2.2008: Hodgkin disease/lymphoma. NCCN Guidelines. v.1.2008: colon cancer.

NCCN Guidelines. v.1.2008: rectal cancer.

Emetogenic Potential of Chemotherapy Agents

Level Agent

High (>90%)

Adriamycin/cyclophosphamide, Cisplatin, Doxorubicin > 60mg/m2

Moderate (30-90%)

Carboplatin, Cyclophosphamide <1500mg/m2, Doxorubicin <60mg/m2, Irinotecan, Ifosfamide <2gm/m2, Temozolomide

Low (10-30%)

Cytarabine 100-200mg/m2, liposomal doxorubicin, etoposide, 5-FU, Methotrexate >50mg/m2-<250mg/m2, Paclitaxel, topotecan

Minimal (<10%)

Aspariginase, Bleomycin, Cetuximab, Rituximab, Vncristine

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. 81

bNeurokinin-1

Nausea and Vomiting Pathophysiology

(Polovich et. al., 2005, reprinted with permission)

Nausea & Vomiting Pharmacologic Management

• Prevention of nausea and vomiting is the goal

• Select appropriate antiemetic based on treatment regimen

• Consider cumulative effects

• Administer through entire anticipated period of nausea & vomiting

• Oral and IV antiemetic 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

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NK-1 Antagonist

■ Indications: – Acute and delayed nausea / vomiting

– Highly emetogenic chemotherapy

■ Common side effects: – Diarrhea, hiccups, fatigue

■ Examples: – Aprepitant (oral)

– Fosaprepitant (IV)

Other agents

■ Corticosteroids - used in combination with other meds. Mechanism of action is unknown

■ Cannabinoids - used for refractory CINV when other agents are ineffective. Many side effects

■ Dopamine antagonists - used for low potential and for breakthrough

■ Benzodiazepines - used for anticipatory CINV and breakthrough

Nausea & Vomiting Non-pharmacologic Management

• Music therapy

• Moderate exercise

• Acupressure

• Acupuncture

• Behavioral interventions

• Dietary interventions

– Small frequent meals, room temperature food (↓ odors)

• Patient education

– Notify if N/V > 24 hrs or unable to maintain fluid intake

– Take antiemetics before arriving

– Follow-up in 24-48 hours

ONS PEP Resource: Chemotherapy-Induced Nausea &

Vomiting ■ Recommended for Practice

– Cannabis/Cannabinoids

– Neurokinin 1 Receptor Antagonist (NK1)

– Serotonin 5HT3 Receptor Antagonist (5HT3)

– Transdermal Granisetron

– Triple Drug Regimen

■ Likely to Be Effective

– Gabapentin

– Hypnosis for Anticipatory CINV

– Managing Patient Expectations

– Olanzapine for breakthrough CINV

– Progesins

– Progressive Muscle Relaxation

– Single Agent Dexamethasone

ONS PEP Resource: Chemotherapy-Induced Nausea &

Vomiting ■ Benefits Balanced with Harm: Virtual Reality

■ Effectiveness Not Established

– Acupressure -Massage/Aromatherapy Massage

– Acupuncture -Metaclopramide (prophylactic)l

– Acstimulation -Mirtazapine

– Electroacupuncture -Olanzapine

– Exercise -Ondansetron as rescue medication

– Ginger -Prochlorperazine for breakthrough N/V

– Grape Juice -Progressive Muscle Relaxation (PMR)

– Guided Imagery -Psychoeducation

– Haloperidol -Thalidomide

– Herbal Medicine -Yoga

■ Effectiveness Unlikely: Cocculine

■ Not Recommended for Practice: Metopimazine

Mucositis: Defined

• Mucositis - Inflammatory process involving the mucous membranes of the oral cavity and gastrointestinal tract

• Stomatitis – inflammatory disease of the mouth.

• Mucosal membranes proliferate with a high turnover rate every 7 – 14 days

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Phases of Mucositis Development Patient Related Assessment Areas for Mucositis

■ Age (very young and very old) – Young recover more quickly ■ Gender (females > males) ■ Poor oral health and hygiene ■ Low body mass index ■ Renal Toxicity (increased creatinine, increased toxicity) ■ Smoking History ■ Previous cancer treatment ■ Hyposalivation (or increased viscosity) ■ Ill-fitting prostheses ■ Hematologic malignancy (to some extent, related to

treatment regimen)

Beck, 2004, Eilers & Million, 2007 Jaroneski, 2006

Risk Factors for Mucositis Regimen-related

• Cytotoxic agent used

• Prolonged or repetitive administration (vs. bolus)

• Radiation therapy to the head/neck region in combination with chemotherapy

• Cumulative radiation dose

• Number of cycles and intensity of treatment

• History of previous episodes of mucositis

• Blood/stem cell transplantation

Agents Most Commonly Associated with Mucositis

• actinomycin D

• amsacrine

• bleomycin

• cytarabine

• daunorubicin

• docetaxel

• doxorubicin

• etoposide

• floxuridine

• 5-fluorouracil

• methotrexate

• mitoxantrone

• plicamycin

• thioguanine

• vinblastine

• vindesine

Mucositis: Consequences

• Pain - *** The hallmark of oral mucositis

• Difficulty swallowing

• Difficulty in communication

• Infection

• Bleeding

• Dose reduction and dose delays

• Increased fatigue

• Increased need nutritional support

Mucositis: Assessment • Perform a thorough oral assessment

– Use a penlight

– Use a gloved finger to gently manipulate tongue and cheek

– Inspect under the tongue and along inner cheeks and gums, inspect hard and soft palate

• Ask the right questions

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Mucositis: Assessment • Subjective:

– pain, burning, increased sensitivity, altered taste, dry mouth

• 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: NCI-CTCAE Grading Scale

Grade Description

Grade 0 (none) None

Grade 1 (mild) Painless ulcers, erythema, or mild

soreness in the absence of lesions

Grade 2 (moderate) Painful erythema, oedema, or ulcers

but eating or swallowing possible

Grade 3 (severe) Painful erythema, oedema, or ulcers

requiring IV hydration

Grade 4 (life-threatening)

Severe ulceration or

requiring parenteral or enteral

nutritional support or prophylactic

intubation

Grade 5 (death) Death related to toxicity

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 • Keep oral cavity clean and moist

– 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, 2009

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

ONS Putting Evidence Into Practice, 2009

ONS PEP Resource: Mucositis

■ Recommended for Practice

– Cryotherapy

– Low Level Laser Therapy

– Oral Care Protocol

– Palifermin

– Sodium Bicarbonate

– Viscous Lidocaine

■ Likely to Be Effective

– Benzydamine

– Lactobacillus Lozenges

– Prophylactic Chlorhexidine

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ONS PEP Resource: Mucositis

Effectiveness Not Established

Allopurinol Mouthwash Flurbiprofen tooth patch Mauka & Kanuka Tetracaine

Aloe Vera Folinic Acid Misoprostol Oral Rinse Tricolsan Mouth Rinse

Amifostine Glutamine Payayor Turmeric

ATL-104 Hangeshashinto Phenylbutyrate rinse Vitamin E

Bethanechol Herbal Medicine Pilocarpine Zinc/Zinc supplements

Ca++ Phosphate Rinse High dose laser therapy Povidone Iodine

Calendula Officinalis Honey Professional Oral Care

Camellia/Wheat Extract Human Intestinal Trefoil Prophylactic CSF

Caphosol Hylauronic Acid Propolis (Bee Glue)

Colchicine Mouthwash Indigowood Root RhEGF

CSF Mouth Rinses Infrared Phototherapy Repifermin

Doxepin Mouthwash Irsogladine Maleate Rhodiola Algida

Fluoride gum Light Therapy Salivary stimulation

ONS PEP Resource: Mucositis

■ Effectiveness Unlikely

– Iseganan

– Traumeel S

– Wobe-Mugos

■ Not Recommended for Practice

– Chlorhexidine (not prophylactic)

– Sucralfate

– Magic Mouthwash

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

• Decreased intake

• Altered or perverted sense of taste for certain

foods

• * Can persist for up to 1 year *

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

■ 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

■ Refer to dietitians for nutritional counseling

■ Assess for weight loss

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

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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

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

In addition to decreasing inflammation, corticosteroids:

a) Improve muscle tone

b) Stimulate weight loss

c) Stimulate the appetite

d) Reduce anxiety

Nursing interventions for the management of nausea include encouraging patients to:

a) Use sauces and gravies

b) Eat foods that are cold or at room temperature

c) Eat high protein / high potassium foods

d) Avoid brushing their teeth when they are nauseated

Cachexia in the patient with cancer may result in increased:

a) Bone density

b) Infection rates

c) Glucose turnover

d) Lipoprotein lipase activity

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Skin Reactions

• Alopecia

• Rash

• Palmar-Plantar Erythrodysesthesia (PPE)

–Also called “Hand-Foot Syndrome”

• Xerosis

• Pruritus

• Paronychia

• Radiation dermatitis

• Radiation recall

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Alopecia

• Chemotherapy-induced most commonly occurs on the scalp

• Extent depends on:

–Mechanism of action of the drug

–Administration route

–Drug dose, serum half-life

–Duration (bolus versus continuous infusion)

–Response of the patient

–Condition of the hair prior to treatment

■ Chemotherapy-Induced

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Risk Factors

• Combination chemotherapy – higher risk

• Epidermal growth factor receptor (EGFR) inhibitors

• High-dose chemotherapy

• Non-cytotoxic medications

• Hypothyroidism

• Aging

• Poor hair condition before cytotoxic treatment

• Concomitant or previous radiation therapy to head

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Chemotherapy Risk of Chemotherapy-Induced Alopecia

Classification High Risk Moderate Risk Low Risk

Alkylating Agent Cyclophosphamide Ifosfamide

Mechlorethamine Methotrexate

Carboplatin Cisplatin

Antimetabolite - Amsacrine Busulfan Cytarabine Gemcitabine

Capecitabine 5-FU Fludarabine Hydroxyurea Thiotepa

Antitumor Antibiotic Daunorubucin Doxorubicin Epirubicin

- Bleomycin Mitoxantrone

Camptothecins Irinotecan Topecan

- -

Epiopdophyllotoxins Etoposide - -

Targeted Therapies - Tyrosine Kinase Inhibitors

Taxanes Docetaxel Paclitaxel

- -

Vinca Alkaloids Vinorelbine - Vincristine Vinblastine

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Degrees of Alopecia

• Grade 1

– Hair loss of <50% of normal for that individual that is obvious only on close inspection

– A different hair style may be required to cover the hair loss but it does not require a wig

• Grade 2

– Hair loss of 50% or greater compared to normal for that individual that is readily apparent to others

– A wig or hair-piece is necessary if the patient desires to completely camouflage the hair loss

– Associated with psychosocial impact

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Expected Time and Pattern of Hair Loss

• Timing: – Hair shedding begins approximately 1-3 weeks after administration

of chemotherapy – May last 1-2 months after initiation of therapy

• Pattern – Hair loss tends to occur first on the crown and sides of head above

ears – Generally reversible

• Regrowth – Begins 1-3 months after discontinuation of therapy – Regrown hair may change in color, structure, or texture – Permanent alopecia after chemotherapy rare • Can occur with high-dose busulfan and cyclophosphamide

– Permanent alopecia after radiation therapy to hair follicles may occur with treatment lasting longer than 4 weeks

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Alopecia Management Prevention

• Scalp hypothermia

– It is practiced and has shown benefit, however, is not FDA approved

–Safety concerns exist for patients with hematologic malignancies

–Further research continues regarding safety and efficacy

• Pharmacologic management

–Little data exists

–Some drugs that may prove beneficial but require further research include topical calcitriol and amifostine

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Alopecia Management

• For Grade 1 and 2 toxicities

–Consider minoxidil 5% twice daily during chemotherapy; biotin 2.5 mg daily, and orthascilic acid 10 mg daily after chemotherapy is completed

–Counsel the patient on the use of hats, scarves, and wigs

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Patient and Family Education

• Cause of alopecia

• Expected timeframe for hair loss and regrowth

• Strategies to manage hair loss and regrowth

–Most strategies have not been tested in clinical trials

–Use shampoos without detergents, menthol, salicylic acid, alcohol, or heavy perfumes

–Avoid permanents, bleach, coloring agents, vigorous brushing, hot rollers, excessive heating with dryer

–Protect scalp from cold and sun (hats, scarves, wigs)

Presentation Title 122

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Local Resources for Support

• The American Cancer Society's program "Look Good...Feel Better“ – Materials available coveringcranial prosthesis (wig) information

and pointers on head coverings. • Website: www.lookgoodfeelbetter.org • Call 1‐800‐395‐LOOK to get a free copy of the catalog

• The American Cancer Society’s Tender Loving Care® publication (both magazine and catalog) – Combines helpful articles and information on any cancer

treatment that causes hair loss. • Website: www.tlcdirect.org • Call 1‐800‐850‐9445 to get a free copy of the catalog

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Epidermal Growth Factor Receptor (EGFR) Rash

• EGFR is normally expressed in the epidermis, sebaceous glands, and hair follicular epithelium

• Plays important role in maintenance of normal skin health

• Inhibition of EGFR believed to cause cutaneous injury and skin rash

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Examples of Epidermal Growth Factor Receptor (EGFR) Inhibitors

• Small molecule targeted therapy

- Erlotinib (Tarceva)

- Lapatinib (Tykerb)

- Vandetanib (Caprelsa)

• Monoclonal antibodies

- Cetuximab (Erbitux)

- Panitumumab (Vectibix)

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Epidermal Growth Factor Receptor (EGFR) Inhibitor Rash

• Resembles acne • Characterized by skin eruption

consisting of: –Papules (small, raised pimples) –Pustules (small pus-filled

blister) • Typically appears on face, scalp,

upper chest, and back • Unlike acne, does not present

with whiteheads or blackheads • Can be symptomatic (itchy or

tender lesions)

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Papular & Pustular Rash

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Papular lesions on chest Follicular Pustules

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Management: Acneiform Rash

• Alcohol-free OTC moisturizing creams or ointments twice daily

• Sunscreen SPF >=15 applied to exposed areas of body and reapply every 2 hours when outside

• Topical low/moderate potency steroid to the face and chest twice daily

• Topical/oral antibiotics or oral low-dose steroids as indicated

■ Low Grade Toxicity Management

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Management: Acneiform Rash

• Stop topical antibiotic if being used

• Begin oral antibiotic for 6 weeks (tetracycline) AND

• Topical low/moderate potency steroid

• Topical low/moderate potency steroid +/-

• Isotretinoin at low doses (20-30mg/day)

■ Severe Toxicity Management

(Rosen, et al., 2014; Memorial Sloan Kettering Cancer Center; 2014a)

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Recommendations for Prevention and Management of EGFR-Inhibitor Rash

MASCC Preventive/Prophylactic • Systemic

• Minocycline 100 mg daily or doxycycline 100 mg BID

• Topical • Hydrocortisone 1% cream with moisturizer

and sunscreen BID Treatment • Topical

• Alclometasone 0.05% cream • Fluocinonide 0.05% cream BID • Clindamycin 1%

• Systemic • Doxycycline 100 mg BID • Minocycline 100 mg daily • Isotretinoin at low doses 20-30 mg/day

NCCN Preventive/Prophylactic • Systemic

• Oral semisynthetic tetracycline agents (doxycycline or minocycline)

• Topical • Hydrocortisone 1%, skin moisturizer and

sunscreen Treatment • Topical

• Topical steroids and antibiotics, such as clindamycin and erythromycin

• Systemic • Oral antibiotics include doxycycline or

minocycline • Systemic steroids are typically not used • Isotretinoin reactively (based on anecdotal

or nonrandomized studies)

Not Recommended: Pimecrolimus 1% cream, tazarotene 0.05% cream, sunscreen as a single agent, tetracycline 500 mg BID, vitamin K, cream, acitretin, oil-in water topical trolamine emulsion

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MASCC: Multinational Association of Supportive Care in Cancer

NCCN: National Comprehensive Cancer Network

. Note: Based on information from Burtness, et al,

2009; Eaby-Sandy et al, 2012; Lacouture, 2011

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What is the mainstay of treatment for a patient experiencing maculopapular rash related to epidermal growth factor receptor inhibitors?

a. Oral steroids, moisturizers, antifungal

b. Topical steroids, antibacterials, and moisturizers

c. Topical benzyl peroxide

d. Discontinuation of the offending agent

Presentation Title 131 /

A patient is experiencing grade 1 alopecia secondary to chemotherapy. Which of the following treatments is most appropriate to

recommend?

a. Scalp hyperthermia

b. Topical calcitriol

c. Amifostine

d. Minoxidil

Presentation Title 132