SUPPORTIVE CARE NATIONAL COMPREHENSIVE CANCER … SLIDES... · National Comprehensive Cancer...

SUPPORTIVE CARENATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) ANTIEMETIC GUIDELINE UPDATES, VERSION 3.2018

MEENAKSHI SHELAT, PHARMD, BCOPDARTMOUTH-HITCHCOCK MEDICAL CENTER

NOVEMBER 2018

DISCLOSURES

• I have nothing to disclose related to the content of this presentation

2

LEARNING OBJECTIVES

• Explain the basic physiology of chemotherapy-induced nausea and vomiting

• Review recent updates that highlight agents/dosages classified as highly emetogenic to ensure adequate guideline-based prophylaxis

• Recognize agents that are categorized as medium, low, and minimal emetogenic risk to recommend appropriate therapy

3

ADDRESSING CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV)

• Need to overcome challenges with implementing guideline-based updates to ensure optimal care for patients experiencing CINV- Education, training, communication, order-sets- Consider patient regimen and clinical, social, financial factors

• Pharmacists play a critical role in education, communication, and counseling

Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar. ASHP 2016.

Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92.4

PHYSIOLOGYMECHANISMS OF ACTION

• Neurokinin 1 receptor antagonist(NK1RA)

• 5-hydroxytryptamine receptor antagonist (5-HT3 RA)

https://www.researchgate.net/figure/Pathophysiology-of-chemotherapy-induced-nausea-and-vomiting_fig2_321927048

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018

5

• NK1 receptor antagonist

• 5-HT3 receptor antagonist

• Dopaminergic receptor antagonist

• Cannabinoid

https://openi.nlm.nih.gov/detailedresult.php?img=PMC4034105_pharmaceuticals-03-02930-g001&req=4

PHYSIOLOGYMECHANISMS OF ACTION


6

TYPES OF EMESIS

Chemotherapy-Induced (Intravenous, IV and Oral, PO)Anticipatory, Acute, Delayed, Breakthrough, Refractory

Radiation-Induced Radiation therapy (RT) Upper abdomen/local sites, Total Body Irradiation (TBI), Chemotherapy and RT


7

PATIENT-FOCUSED GOAL:PREVENTING NAUSEA AND VOMITING

≤ 24 hrsAcute

High

Moderate

> 24 hrsDelayed


8

PATIENT CASE AND DISCUSSION

• Pt ND is a 62 year old femaleStage IIIC1 grade 2 endometrial cancer, s/p robotically assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node dissection

• Past medical history: reports low alcohol intake

• Plan to start paclitaxel 175 mg/m2 and carboplatin AUC 5, followed by pelvic radiation therapy 50 Gy or 45 Gy with cisplatin for chemosensitization, with further chemotherapy to follow

9

CINV IS MULTIFACTORIAL

• Emetogenic risk of agents in regimen (high, moderate, low, minimal)

• Female

• Younger age (less than 50 yrs)

• History of low alcohol intake

• History of motion sickness

• History of emesis during pregnancy

Heskith P. Oncologist. 1999; 4:191-6.National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar. ASHP 2016.Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92.

10

DRUG CLASSESClass NK1 receptor

antagonist 5‐HT3 receptor antagonist Corticosteroids Thiobenzodiazepine

Examples aprepitant‐ injectable emulsion‐ oral (PO)fosaprepitant‐ intravenous (IV)netupitant (PO)rolapitant (PO)

ondansetronpalonosetron (IV)granisetron‐ subcutaneous (SQ) ‐ intravenous‐ transdermaldolasetron oral

dexamethasone (dex) olanzapine (PO)

netupitant/palonosetron (PO)fosnetupitant/palonosetron (IV)

Monitoring/Common Side Effects

CYP3A4 inhibitor dex dose reductionNote: rolapitant is not a CYP3A4 inhibitor or inducer

HeadacheConstipationQTc/Cardiac

Insomnia HyperglycemiaDyspepsia

CNS depression, sedationWeight gainOrthostatic hypotensionQTcInteraction‐ metoclopramide/ haloperidol – EPS

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018Roila, F. et a. Annals of Oncology, Volume 27, Issue suppl_5, 1 September 2016, Pages v119–v133

11

OTHER DRUG CLASSES/PATHWAYSClass Benzodiazepine Cannabinoid Phenothiazine Dopaminergic

receptor antagonistExamples lorazepam dronabinol

nabiloneprochlorperazinepromethazine

metoclopramide*haloperidol**

Monitoring/Common Side Effects

CNS depressionUseful for anxiety

CNS depressionMay help appetite

Increased risk of EPSCNS depressionSedation: promethazine >prochlorperazine

Increased risk of EPSQTc

*Diarrhea, but helps gastroparesis*Tardive dyskinesia

**CNS depression


12

RECENT CLINICAL TRIALS AND PAPERS

Trial Efficacy Safety

A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy.

Yanai T et al, Int J Clin Oncol. 2018 Apr;23(2):382-388.

Benefit in delayed emesis 5 mg (CR 85.7%, P < 0.001) 10 mg (CR 77.6%, P = 0.01)

Somnolence 5 mg: 45.5% 10 mg: 53.3%

Papers

Gilmore, J et al, Recent advances in antiemetics: new formulations of 5HT3-receptor antagonists. Cancer ManagRes. 2018 Jul 3;10:1827-1857.

Navari, R et al, Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. Onco Targets Ther. 2018; 11: 6459–6478.

13

TYPES OF EMESIS

Chemotherapy-Induced (Intravenous, IV and Oral, PO)Anticipatory, Acute, Delayed, Breakthrough, Refractory

Radiation-Induced Radiation therapy (RT) Upper abdomen/local sites, Total Body Irradiation (TBI), Chemotherapy and RT


14

UPDATES REGARDING AGENTS AND REGIMENSType of Emesis/Emetic Risk

Agent Formulation

High cisplatincarboplatin ≥ 4anthracycline/cyclophosphamideTransplant regimen such as CBV

IVIVIVIV

Moderate to High enasidenibmidostaurinniraparib

POPOPO

Moderate liposomal encapsulation cytarabine and daunorubicin IV

Low olaratumab IV

Minimal to Low abemaciclibbrigatinibnertainibribociclib

POPOPOPO

Minimal avelumabrituximab and hyaluronidase

IVSQ


15

REFER TO MOST UPDATED VERSION OF GUIDELINES: INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN)Type of Emesis/Emetic Risk

Day 1 Subsequent Days Days 2,3,4 for high; Days 2,3 for moderate

CINV – High NK1RA + 5-HT3 RA + dex olanzapine + palonosetron + dex olanzapine + NK1RA + 5-HT3 RA + dex

aprepitant PO if PO used Day 1 or ***dex olanzapine aprepitant PO if PO used Day 1,

olanzapine + dex

CINV - Moderate 5-HT3 RA + dex olanzapine + palonosetron + dex 5-HT3 RA + dex (± NK1RA)

5-HT3 RA*** or dex olanzapine aprepitant PO if PO used Day 1 ± dex

CINV - Low dex metoclopramide prochlorperazine 5-HT3 RA

CINV - Minimal No routine prophylaxis regimen

RT – localTBIChemo and RT

granisetron PO daily or ondansetron PO BID ± dex granisetron PO daily or ondansetron PO BID/TID ± dex See above

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. Journal of Oncology Practice 2017 13:12, 825-830

*** May not be needed

16

REFER TO MOST UPDATED VERSION OF GUIDELINES: INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN)

Type of Emesis,Emetic Risk

Day 1 Subsequent Days Days 2,3,4 for high; Days 2,3 for moderate

CINV High

NK1RA + 5-HT3 RA + dex olanzapine + palonosetron + dex olanzapine + NK1RA + 5-HT3 RA + dex

aprepitant PO if PO used Day 1 or ***dex olanzapine aprepitant PO if PO used Day 1, olanzapine + dex

CINV Moderate

5-HT3 RA + dex olanzapine + palonosetron + dex 5-HT3 RA + dex (± NK1RA)

5-HT3 RA*** or dex olanzapine aprepitant PO if PO used Day 1 ± dex


*** May not be needed

17

REFER TO MOST UPDATED VERSION OF GUIDELINES: INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN)

Type of Emesis,Emetic Risk

Day 1

CINVLow

Dex Metoclopramide Prochlorperazine 5-HT3 RA

CINVMinimal

No routine prophylaxis regimen

Radiation Therapy (RT)RT – localTBIChemo and RT

Granisetron PO daily or ondansetron PO BID ± dex Granisetron PO daily or ondansetron PO BID/TID ± dex See respective emetic risk of agents


18

PATIENT CASE AND DISCUSSION

• Pt ND is a 62 year old femaleStage IIIC1 grade 2 endometrial cancer, s/p robotically assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node dissection

• Past medical history: reports low alcohol intake

• Plan to start paclitaxel 175 mg/m2 and carboplatin AUC 5, followed by pelvic radiation therapy with cisplatin for chemosensitization, with further chemotherapy to follow

19

KEY TAKEAWAYS

• Consider patient clinical scenario and use clinical judgment to ensure appropriate coverage for chemotherapy or radiation therapy-induced nausea/vomiting- Recognize risk factors - Determine emetic risk of intravenous or oral chemotherapy agents/regimen- Apply guideline-based updates when possible- Consider drug interactions- Monitor side effects- Assess what agents work and/or try a different class or pathway

Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar. ASHP 2016.

Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92.


POST-LECTURE QUESTIONSWhich of the following are risk factors for chemotherapy-induced nausea/vomiting (CINV)?

a) Younger age (less than 50 yrs) b) Female c) History of low alcohol intake d) all of the above

21

POST-LECTURE QUESTIONS

For highly emetogenic chemotherapy agents, recent updates showed that the addition of what agent to prophylaxis helps to decrease the chance of nausea in adults and can also be used for breakthrough nausea/vomiting?

a) Diphenhydramine

b) Olanzapine

c) Lorazepam

d) Metoclopramide

22

POST-LECTURE QUESTIONS

For highly emetogenic chemotherapy agents, including for carboplatin with AUC ≥ 4, a recent update showed that the addition of what class of agents to prophylaxis helps to decrease the chance of nausea in adults (also can be used in pediatrics)?

a) GABA receptor antagonist

b) Serotonin receptor antagonist

c) Neurokinin 1 receptor antagonist

d) H2 Antihistamine

23

SUPPORTIVE CARENATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) ANTIEMETIC GUIDELINE UPDATES, VERSION 3.2018

MEENAKSHI SHELAT, PHARMD, BCOPDARTMOUTH-HITCHCOCK MEDICAL CENTER

NOVEMBER 2018

SUPPORTIVE CARE NATIONAL COMPREHENSIVE CANCER … SLIDES... · National Comprehensive Cancer...

Documents

Transcript of SUPPORTIVE CARE NATIONAL COMPREHENSIVE CANCER … SLIDES... · National Comprehensive Cancer...