up-to-date management of chemotherapy induced nausea and vomiting
TRANSCRIPT
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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.