Thanks for your participation

UP-TO-DATE MANAGEMENT OF CHEMOTHERAPY INDUCED NAUSEA

AND VOMITING

DR.TAREQ SALAH,MDLECTURER OF CLINICAL ONCOLOGY

ASSIUT FCULTY OF MEDICINEESMO Accreditation certificate

Magnitude of the problem..

Everyday Case Scenario

• Female Patient,45 years old.

• Rt Breast cancer Stage II ,TNBC.

• Scheduled for adjuvant Chemotherapy 4AC—-12XP/w.

• Received Her 1st chemo 21 days ago and her 2nd chemotherapy is today.

• She suffered considerable Nausea and vomiting after 2 days of the first chemo that required ER admission and Intravenous fluids.

• Just upon entry to hospital she started to vomit.

• Is there a relation? Future management?

IMPORTANT DEFINATIONS

TYPES OF CINV

Similar but not the same

TYPES OF CINV

• JUST TO MAKE IT SIMPLE..

TIMING AETIOLOGY

BREAKTHROUGHDELAYEDACUTE ANTICIPATORY

As regard Timing:

PATHOPHYSIOLOGY

Pathophysiology

Biphasic pattern of emetic intensity

Acute phase

Pathophysiology

Delayed

ALWAYS REMEMBER DRUGS USED ARE A TEAM NOT COMPITITORS..

As regard aetiology:

RISK FACTORS FOR CINV

RISK FACTORS

• PATIENT RELATED.

• REGIMEN RELATED.

PATIENT RELATED

The most worrying Side effects of chemotherapy

• Alopecia.

• Vomiting.

• Infection.

• Nausea.

• Weight loss.

Regimen related

Classification of regimens according to severity

Emetogenic potential of chemotherapeutic

REGIMEN RELATED

REGIMEN RELATED

Other factorsfew studies have accounted for important treatment- and patient-related variables, such as • Chemotherapy dose.• Dose Rate .• Route of administration.• Gender. • Age .• History of ethanol consumption.

OVERALL RISK=PATIENT RELATED

RISK + REGIMEN RELATED RISK

SO OVERALL RISK IS NEVER TO BE LESS THAN REGIMEN RELATED RISK

I’ll treat in the old school!

Tumor Type emetogenic chemotherapy

Incidence of nausea and

vomiting

Lung cancerGemcitabine/CaroplatinPaclitaxel/Carboplatin

Docitaxel/Carboplatin

69%59%

42%

Lymphoma CHOP 50%

Colon FOLFOX4FOLFIRI

65%50%

Breast TCAC

14%42%

Risk of CINV30-90%

Highly emetogenic regimens5HT-3 antagonist +

Dexamethazone

75% of patients will experience CINV

moderately emetogenic regimens

5-HT3 antagonist + Dexamethazone

58% of patients will experience CINV

Long way !

Then came the Aprepitantera…

ESMO CLASSIFY MANAGEMENT OF CINV

Before Aprepitant After Aprepitant

Then Phase III Studies…

i.e. Compared to standard thx at that time

Standard

Experimental

Day 1 Day 2,3,4

ondansetron 32 mg+ dexamethasone 20 mg

dexamethasone 8 mg twice a day on days 2–4 +ondansetron 32 mg

aprepitant 80 mg on days 2 and 3

+ dexamethasone 8 mg daily on

days 2–4

aprepitant 125 mg on day 1+ Dexamethasone 12 mg

The dexamethasone dose was reduced in the aprepitant arms because a pharmacokinetic

study found that aprepitant increased dexamethasone plasma concentrations

resulting in an approximately twofold increase in AUC .

The primary endpoint was complete response (no emesis, no use of rescue antiemetics) over

the 5-day study period. In all three studies complete response was

significantly superior with aprepitant (73% versus 52%, P < 0.001; 63% versus 43%, P < 0.001;

72% versus 61, P < 0.003).

ESMO GL 2010

14 - 20% Absolute

gain

GENERAL RULES OF MANAGEMENT

GUIDELINES !

Highly emetogenic Moderately emetogenic

<24 hAcute

>24 hdelayed

<24 hAcute

>24 hdelayed

ANTICIPATORY BREAKTHROUGHACUTEDELAYED

LORAZEPAM PREMEDICATIONPRESCRIPTION

PRESCRIPTION

Casopitant

• Nk1 antagonist.• GlaxoSmithKline decided to discontinue the

regulatory filings for casopitant.

MASCC ESMO ASCO NCCN ONS

Highly emetogeni

c

Moderately emetogenic (Considered

highly emetogenic

)Other

moderately

emetogenic

3 randomised controlled trials.granisterone + dexamethasone

Rolapitant+ granisterone + dexamethasone

• Rolapitant inhibits the CYP2D6 enzyme. • Rolapitant is contraindicated with the use

of thioridazine because use of the 2 drugs together may increase the amount of thioridazine in the blood and cause an abnormal heart rhythm that can be serious.

• The most common side effects in patients treated with rolapitant include neutropenia, hiccups, decreased appetite, and dizziness.

Take home message

• CINV is very worrying side effect.

• Best management is prevention from the start.

• It is a standard in highly emetogenic chemotherapy regimens.(+AC).

• ? in moderately emetogenic regimens and not in mildly emetogenic chemotherapy.

• Not in mild or minimal emetogenic.