up-to-date management of chemotherapy induced nausea and vomiting
TRANSCRIPT
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Thanks for your participation
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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
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Magnitude of the problem..
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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?
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IMPORTANT DEFINATIONS
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TYPES OF CINV
Similar but not the same
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TYPES OF CINV
• JUST TO MAKE IT SIMPLE..
TIMING AETIOLOGY
BREAKTHROUGHDELAYEDACUTE ANTICIPATORY
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As regard Timing:
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PATHOPHYSIOLOGY
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Pathophysiology
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Biphasic pattern of emetic intensity
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Acute phase
Pathophysiology
Delayed
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ALWAYS REMEMBER DRUGS USED ARE A TEAM NOT COMPITITORS..
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As regard aetiology:
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RISK FACTORS FOR CINV
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RISK FACTORS
• PATIENT RELATED.
• REGIMEN RELATED.
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PATIENT RELATED
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The most worrying Side effects of chemotherapy
• Alopecia.
• Vomiting.
• Infection.
• Nausea.
• Weight loss.
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Regimen related
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Classification of regimens according to severity
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Emetogenic potential of chemotherapeutic
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REGIMEN RELATED
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REGIMEN RELATED
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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.
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OVERALL RISK=PATIENT RELATED
RISK + REGIMEN RELATED RISK
SO OVERALL RISK IS NEVER TO BE LESS THAN REGIMEN RELATED RISK
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I’ll treat in the old school!
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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%
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Highly emetogenic regimens5HT-3 antagonist +
Dexamethazone
75% of patients will experience CINV
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moderately emetogenic regimens
5-HT3 antagonist + Dexamethazone
58% of patients will experience CINV
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Long way !
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Then came the Aprepitantera…
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ESMO CLASSIFY MANAGEMENT OF CINV
Before Aprepitant After Aprepitant
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Then Phase III Studies…
i.e. Compared to standard thx at that time
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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
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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 .
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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
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14 - 20% Absolute
gain
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GENERAL RULES OF MANAGEMENT
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GUIDELINES !
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Highly emetogenic Moderately emetogenic
<24 hAcute
>24 hdelayed
<24 hAcute
>24 hdelayed
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ANTICIPATORY BREAKTHROUGHACUTEDELAYED
LORAZEPAM PREMEDICATIONPRESCRIPTION
PRESCRIPTION
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Casopitant
• Nk1 antagonist.• GlaxoSmithKline decided to discontinue the
regulatory filings for casopitant.
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MASCC ESMO ASCO NCCN ONS
Highly emetogeni
c
Moderately emetogenic (Considered
highly emetogenic
)Other
moderately
emetogenic
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3 randomised controlled trials.granisterone + dexamethasone
Rolapitant+ granisterone + dexamethasone
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• 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.
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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.
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