chemotherapy-induced nausea and vomiting (cinv ... cinv... · breast cancer case study •58 y/o...

Chemotherapy-Induced Nausea and Vomiting (CINV):

Strategies for Optimizing Oncology Nursing Care

Beth Eaby-Sandy, MSN, CRNP, OCN

Educational Objectives

• Describe the primary pathways that result in CINV

• Identify appropriate therapeutic options to address specific types of CINV

• Utilize educational tactics to help patients improve CINV outcomes

Breast Cancer Case Study

• 58 y/o female presents to oncology clinic after mastectomy with lymph node dissection. She had a 2.3cm ductal carcinoma of the L breast with 2 positive axillary nodes. Her tumor is HER2 negative, ER/PR +.

• PET/CT scan and MRI brain are negative for metastases.

• She is a married mother of 2 grown children and she has a 3-year-old grandson whom she watches 2 days a week to help her daughter with childcare expenses.

Breast Cancer Case Study cont.

• PMH: minor HTN, thyroid cancer in her 20’s, post thyroidectomy

• PSH: she smoked 1 PPD for 15 years, quit at age 30, and drinks socially, about one drink per week

• She is depressed about diagnosis, anxious about side effects of chemotherapy including nausea and hair loss

• Also concerned about her ability to care for her grandson 2 days a week (Thursdays and Fridays)

Breast Cancer Case Study cont.

Patient will receive three sequential chemotherapy regimens

Initial treatment Second treatment Third treatment

Dose dense doxorubicin (60mg/m2) with cyclophosphamide (600mg/m2) every 2 weeks for 4 cycles

Paclitaxel 175mg/m2 every 2 weeks for 4 cycles

Anastrazole for 5 years

Scope of the Problem Chemotherapy-Induced Nausea and Vomiting (CINV)

• CINV is among the most common, unpleasant, and feared side effects of chemotherapy

• Approximately 70% - 80% of all patients who receive chemotherapy experience nausea or vomiting

• CINV can be prevented in 70% - 80% of patients with the application of evidence-based treatment guidelines

Hesketh PJ. N Engl J Med. 2008;358:2482-2494. Richardson J, et al. Eur J Cancer Care. 2007;16:402-412. Jordan K, et al. Oncologist. 2007;12(9):1143-1150.

Poorly Controlled CINV

• Leads to:

– Weight loss (or gain)

– Life threatening complications: dehydration, electrolyte imbalances, GI perforation, bleeds, aspiration

– Decrease in quality of life

– Anticipatory CINV

Bloechl-Daum B, et al. J Clin Oncol. 2006;24:4472–4478.

Reported Negative Impact of CINV on Daily Activities

12%

19%

23%

33%

33%

35%

47%

Taking medications

Caring for Others

Work/Employement

Time with Friends

Running Errands

Household Tasks

Eating Meals

% preventedfrom participatingin daily activities

Lindley CM, et al. Qual Life Res. 1992;1(5):331-340.

Risk Factors

CINV

Factors Contributing to CINV: Chemotherapy

Emetogenic Potential of Agents

NCCN Guidelines. Version 1.2015, 06/18/14 © National Comprehensive Cancer Network, Inc. 2014.

High >90%

Moderate 30% - 90%

Low 10% - 30%

Minimal <10%

High Emetogenic Chemotherapy (HEC) >90% Without Antiemetics

• AC combination

– Doxorubicin or epirubicin with cyclophosphamide

• Cisplatin (any dose)

• Carmustine >250 mg/m2

• Cyclophosphamide ≥1,500 mg/m2

• Dacarbazine

• Doxorubicin >60mg/m2

• Epirubicin >90mg/m2

• Ifosfamide >2g/m2 per dose

• Mechlorethamine

• Streptozotocin

NCCN Guidelines. Version 1.2015, 06/18/14 © National Comprehensive Cancer Network, Inc. 2014.

Moderate Emetogenic Chemotherapy (MEC) 30% – 90% Without Antiemetics

• Aldesleukin >12-15 million IU/m2

• Amifostine >300mg/m2

• Arsenic trioxide

• Azacitidine

• Bendamustine

• Busulfan

• Carboplatin*

• Carmustine* ≤250mg/m2

• Clofarabine

• Cytarabine >200 gm/m2

• Cyclophosphamide <1,500 mg/m2

• Dactinomycin*

• Daunirubicin*

• Doxorubicin* <60mg/m2

• Epirubicin* <90mg/m2

• Idarubicin

• Ifosfamide* <2000mg/m2

• Interferon alfa ≥10 million IU/m2

• Irinotecan*

• Melphalan

• Methotrexate* ≥250mg/m2

• Oxaliplatin

• Temozolomide

*May be highly emetogenic in certain patients

NCCN Guidelines. Version 1.2015, 06/18/14 © National Comprehensive Cancer Network, Inc. 2014.

Factors Contributing to CINV: Patient

• Female1,2

• Age <50 years2

• History of low alcohol intake (<1.5oz/day)1,2

• History of prior CINV1,2

• History of motion sickness2

• History of morning sickness2

• Anxiety3

1. Hesketh PJ. Oncologist. 1999;4(3):191-196. 2. Navari RM, et al. J Support Oncol. 2003;1(2):89-103. 3. NCCN Guidelines. Version 1.2015, 06/18/14 © National Comprehensive Cancer Network, Inc. 2014.

Breast Cancer Case Study

• Risk factors for our patient:

– AC regimen, high risk chemotherapy

– Female

– Over age 50, though not much

– Anxiety

• What are her social barriers and issues?

– Active lifestyle

– Cares for grandson

Understanding Pathophysiology

CINV

Hesketh PJ. N Enl J Med. 2008;358:2482-2494. Apfel CC. Anasthesiol Intensivmed Notfallmed Schmerzther. 2005;40(8):497-503.

The Pathophysiology of CINV

• A complex interaction involving receptors and neurotransmitters located in – Brain stem

– Gastrointestinal tract

– Cortical and limbic systems

The Pathophysiology of CINV: GI Enteric Nervous System/Peripheral

• Vagal and sympathetic: Visceral pathways

• Receptors in close proximity to the enteroendocrine cells of the GI mucosa and proximal small intestine

• Stimulated by direct mucosal or blood borne mechanisms

• Afferent impulse terminates in the NTS

• Primarily mediated by 5-HT3 and NK-1

• Vagal: Dependent pathway is primary mechanism for acute CINV

Hesketh PJ. N Engl J Med. 2008;358:2482-2494. Hawkins R, et al. Clin J Oncol Nurs. 2009;13(1):54-64.

1. Hesketh PJ. N Engl J Med. 2008;358:2482-2494.

How will we prevent CINV in our patient?

Goals of Treatment

• Prevention, rather than reaction, is key

• Minimize CINV by using optimal medications

• Choose regimen that will minimize side effects of the antiemetics in each particular patient

• Have rescue medications on hand at home

• Mediated primarily by serotonin

• Related to emetogenic potential of the regimen

• Intensity peaks at 5 - 6 hours

• Pharmacological management is primary strategy

Delayed 24 hours to 7

days

Anticipatory – Occurs before drug administration

Refractory and breakthrough

C

H

E

M

O

T

H

E

R

A

P

Y

• Substance P plays the primary role • Effective management of acute CINV will reduce

the severity • More common with long half-life • Cisplatin is the most common drug with peak

intensity at 48 - 72 hours

• Experiential; more difficult to control, ongoing

• Nausea is more common than vomiting

• Effective treatment of acute and delayed CINV is key

Ongoing; may be a result of underlying processes

Hesketh PJ. N Engl J Med. 2008;358:2482-2494. Hawkins R, et al. Clin J Oncol Nurs. 2009;13(1):54-64.

Kris MG, et al. J Clin Oncol; 2006;24:2932-2934.

Breast Cancer Case Study cont.

• What antiemetic regimen will be right for our patient receiving dose dense AC?

– Following the guidelines, NCCN

• What prescriptions should she have at home for CINV?

Ondansetron 1991

Granisetron 1993

Palonosetron 2003

Granisetron Transdermal

2008

Aprepitant Oral 2003

Fosprepitant IV

2008

Netupitant/ Palonosetron

PO 2014

*NK-1 receptor antagonists approved with steroids and 5-HT3 RA

History of Antiemetics1-8

1. Schwartzberg L. J Support Oncol. 2006;4(2 Suppl 1):3-8.; 2. Frame DG. J Support Oncol. 2010;9;8(2 Suppl 1):5-9.; 3. Zofran (ondansetron hydrochloride) Full Prescribing Information. GlaxoSmithKline Research Triangle Park, NC ;2014; 4. Kytril (granisetron hydrochloride) Full Prescribing Information. Genentech USA. San Francisco, CA. 2011 ; 5. Aloxi (palonosetron hydrochloride) Full Prescribing Information. Eisai Inc., Woodcliff Lake, NJ. 2014.; 6. Sancuso (granisetron transdermal patch) Full prescribing information. ProStrakan Inc., Bridgewater, NJ. 2014.; 7. Emend (aprepitant) Full Prescribing Information. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ. 2014; 8. Emend (fosaprepitant dimeglumine) Full Prescribing Information. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ. 2014.

Rolapitant 2015

Classes of Agents for CINV Prevention

5-HT3 RA

–Dolasetron

–Granisetron

–Ondansetron

–Palonosetron

NK-1 RA

– Aprepitant

– Fosaprepitant

– Netupitant

• combination tab with palonosetron

– Rolapitant

• approved Sept. 2015

Other Classes of Agents for CINV

• Corticosteroids: dexamethasone is most used

• Metoclopromide

• Benzodiazepines: lorazepam, alprazolam, midazolam

• Dopamine RAs: prochlorperazine, haloperidol

• Cannabinoids: dronabinol, nabilone

Newer Agents: Netupitant/Palonosetron (NEPA)

• First combined tablet of an NK-1 RA netupitant (300mg) with oral 5-HT3 RA palonosetron (0.5mg) – One capsule taken 1 hour prior to chemotherapy (with

or without food)

• 3 large trials looked at NEPA + dex in highly and moderately emetogenic chemotherapy regimen vs oral palonestron + dex – NEPA + dex showed improvement in CR* in treating

CINV over oral palonosetron + dex

Jordan K, et al. 2015. Annals of Oncology. 2015. Available at http://annonc.oxfordjournals.org/.

* CR = complete response

Newer Agents: NEPA (continued)

• Safety study – NEPA + dex vs. oral palonosetron + dex + aprepitant

– Comparable safety profile in both arms

• Offers a different route for potential convenience for the patient as well as infusion suite

• NEPA is a tablet and CYP 3A4 inhibitor so should be used cautiously with other drugs metabolized this way. – Dexamethasone is example, should reduce the dose of

dex when given with NEPA

Jordan K, et al. 2015. Annals of Oncology. 2015. Available at http://annonc.oxfordjournals.org/.

Newly Approved Agent: Rolapitant

• Oral NK-1 RA approved Sept. 2015 by FDA for treatment of CINV – 180-hr half-life (7.5 days)

• Trialed with IV granisetron/dex vs granisetron/dex alone – Found to be superior in arm with the rolapitant

• Does not inhibit CYP 3A4 pathway, so good to avoid drug-drug interactions

• May be good for multiday regimens as well given long half-life

Jordan K, et al. 2015. Annals of Oncology. 2015. Available at http://annonc.oxfordjournals.org/.

Old Drug, New Use: Olanzapine

• Used as atypical antipsychotic, but exhibits antiemetic properties

• Targets multiple receptors: dopaminergic, serotinergic, adrenergic, histaminergic, muscarinic

• Trialed and found to be comparable in the prophylactic and breakthrough settings

• Some side effects of somnolence, hypotension, constipation, dizziness, fatigue, dyspepsia and restlessness – None were grade 3 or 4 toxicities

Jordan K, et al. 2015. Annals of Oncology. 2015. Available at http://annonc.oxfordjournals.org/.

CINV Guidelines

• Guidelines are based on evidence, formulated by experts who review clinical trials

• NCCN, ASCO, MASCC/ESMO, ONS

• Inadequate treatment of CINV leads to higher healthcare costs and patient suffering

• Adherence to guidelines leads to better outcomes for CINV

Viale PH, et al. Clin J Oncol Nurs. 2012;16 (4):E133-41. Aapro M, et al. Ann Oncol. 2012;23:(8):1986-1992.

NCCN Guidelines for HEC

• NK-1 RA (aprepitant tri-pack or fosaprepitant)

• + • 5-HT3 RA

(dolasetron/granisetron/ondansetron/palonosetron)

• + • Dexamethasone 12mg PO/IV

day 1 – Dexamethasone 8mg

day 2-4

• Netupitant/palonosetron tablet day 1

• + • Dexamethasone 12mg PO/IV

day 1 – Dexamethasone 8mg

day 2-4

• Olanzapine 10mg day 1-4

• + • Palonosetron IV

• + • Dexamethasone 20mg IV

day 1

Option A

Option B

Option C

NCCN Guidelines for Antiemesis. Version 1.2015.

Breast Cancer Case Study cont.

• Want to be sure she is receiving NK-1 RA + 5-HT3 RA + Dex – Oral regimen versus IV regimen? – Long acting NK-1 RA and/or long acting 5-HT3 RA – Dex taper per guidelines, or not?

• Want to be sure she has something at home for breakthrough CINV

• How will we assess if our antiemetic treatment is effective?

• What possible side effects could she have from the antiemetics?

Patient Barriers and Misconceptions to CINV treatment

Salsman JM, et al. NCCN J Natl Compr Canc Netw. 2012;10(2):149-157.

CINV is part of treatment; don’t want to be a complainer

Don’t want to be perceived as weak; need to be strong

Do not want to take more medications; fear side effects

Feared cost

Communication barriers with the oncology provider

Fear healthcare provider may withhold chemotherapy

CINV means treatment is working

Provider Barriers and Misconceptions to CINV treatment

Grunberg SM, et al. Cancer. 2004;100(10):2261-2268. Salsman JM, et al. NCCN J Natl Compr Canc Netw. 2012;10(2):149-157. .

Underestimation of CINV, especially delayed

Communication with the patient

Feared cost to patient

Fear of side effects of antiemetics to the patient

CINV treatment might interfere with other medications

Limit number of medications

CINV may be phenotypic marker for response

How can nurses ensure patient gets correct antiemetics?

• Know the patient and risk factors

• Be knowledgeable on guidelines and available medications

• Develop protocols

– Standard order sets on EMR

• Consider use of tools to assess CINV or diaries

Cunningham R. 2010. Medscape http://www.medscape.org/viewarticle/730000

Patient Education Techniques

• Oncology nurses are best poised to educate patients about CINV

• Clear written instructions on how to take prophylactic and as needed antiemetics

• Using diaries or phone calls to document CINV between office visits

• Be sure that patient has appropriate contact information to the office

• Educate on when is appropriate to call office about N/V

Young A, et al. ecancer 2013, 7:296 DOI: 10.3332/ecancer.2013.296.

Key Clinical Take-Aways

• CINV continues to be an important aspect of supportive oncology care that, when not well controlled, has significant consequences

• Understanding pathways will help guide treatment options

• Following evidence-based guidelines is critical to optimal management of CINV

• Several medications and combinations are available for use

• There continues to be active research looking into new medications and pathways to prevent and treat CINV