Transcript

JØRN HERRSTEDT, M.D.COPENHAGEN UNIVERSITY HOSPITAL

HERLEV, DENMARK

CHEMOTHERAPY-INDUCED ACUTE EMESIS

SCIENTIFIC SESSION: THE PERUGIA CONSENSUS ON NAUSEA AND VOMITING

June 2004

PERUGIA 2004 ANTIEMETIC GUIDELINES- Committees and their Areas

I. Emetic classification of antineoplastic agents

II. Acute emesis: Highly emetic chemotherapy

IV. Acute emesis: Moderately emetic chemotherapy

VI. Emesis induced by minimal or low emetic risk chemotherapy

June 2004

PARTICIPANTS IN THE PERUGIA ANTIEMETIC COMMITEES I, II, IV and VI

Enzo Ballatori, PhDSussanne Borjeson, RN, PhDRebecca Clark-Snow, RN, BSN, OCNAlbano Del Favero, MDLawrence Einhorn, MDRichard Gralla, MDSteven Grunberg, MDJørn Herrstedt, MDPaul Hesketh, MD

Jim Koeller, RPh, MS

Mark Kris, MD

David Osoba, MD

Bernardo Rapoport, MD

Cynthia Rittenberg, RN, MN, AOCN

Fausto Roila, MD

Maurizio Tonato, MD

David Warr, MD

DEFINITION OF

ACUTE EMESIS

June 2004

Time course of emesis following cisplatin with a 5-HT3- or NK1 RAPatients with no emesis (%)

Time (h) since initiation of cisplatin

0 8 24 40 60 80 100 1200

20

40

60

80

100 GRA + DEX + PLA5 days Aprepitant + GRA + DEX6 days Aprepitant + DEX + PLA5 days Aprepitant + DEX + PLA

Hesketh PJ et al. Eur J Cancer 2003;39:1074-80.

DEFINITION OF

EMETIC RISK

June 2004

PERUGIA 2004 ANTIEMETIC GUIDELINES

ANTIEMETIC TREATMENT GUIDELINES- Committee I (1/5): The Four Emetic Risk Groups -

Fewer than 10% at risk

Risk in 10% to 30% of patients

Risk in 30% to 90% of patients

Risk in nearly all patients (> 90%)

MINIMAL

LOW

MODERATE

HIGH

Multinational Association of Supportive Care in Cancer June 2004

June 2004

COMMITTEE II and IV- Principles of Care for Acute Highly and Moderately Emetic Settings -

UNANIMOUS CONSENSUS: CATEGORY I EVIDENCE

- Use the lowest tested fully effective dose

- No schedule is better than a single dose givenbefore chemotherapy

- The antiemetic efficacy and adverse effects of theseagents are comparable in controlled trials

- Intravenous and oral formulations are equally effectiveand safe*

- Always give dexamethasone with a 5-HT3 antagonistbefore chemotherapy

* Palonosetron has only been investigated as an IV formulation.

Multinational Association of Supportive Care in Cancer June 2004

June 2004

ANTIEMETIC TREATMENT GUIDELINESCommittee I: Emetic Risk Groups – High Risk

Single IV agents

Single oral agents

CisplatinMechlorethamineStreptozotocinCyclophosphamide > 1500 mg/m2CarmustineDacarbazine

HexamethylmelamineProcarbazine

June 2004

COMMITTEE II:

Guideline for the Prevention of Acute Nausea and VomitingFollowing Chemotherapy of High Emetic Risk:

To prevent acute vomiting and nausea following chemotherapyof high emetic risk, a three-drug regimen including single dosesof a 5-HT3 antagonist, dexamethasone, and aprepitant givenbefore chemotherapy is recommended.

MASCC Level of Consensus: HighMASCC Level of Confidence: High

ASCO Level of Evidence: IASCO Grade of Recommendation: A

June 2004Multinational Association of Supportive Care in Cancer

June 2004

ANTIEMETIC TREATMENT GUIDELINES- Committee I: Emetic Risk Groups – Moderate Risk

Single IV agents OxaliplatinCytarabine > 1 gm/m2CarboplatinIfosfamideCyclophosphamide < 1500 mg/m2DoxorubicinDaunorubicinEpirubicinIdarubicinIrinotecan

Single oral agents CyclophosphamideEtoposideTemozolomideVinorelbineImatinib

June 2004

COMMITTEE IV (1/3):

Guideline for prevention of acute emesis in moderately emetic chemotherapy (MEC):

A 5-HT3 receptor antagonist plus dexamethasoneis recommended for prophylaxis of acute nauseaand vomiting in the first course of MEC.

MASCC level of confidence: HighMASCC level of consensus: High

ASCO level of evidence: IASCO grade of recommendation: A

Multinational Association of Supportive Care in Cancer June 2004

June 2004

Palonosetron Phase III studies Acute phase

NS67%OndansetronHigh

Palo superior0%OndansetronModerate

NS4-6% DolasetronModerate

CRDexComparatorEmetic risk group

June 2004

COMMITTEE IV (2/3):

Guideline for prevention of acute emesis in moderately emetic chemotherapy:

There are no clinically relevant differences in the effectiveness of the 5-HT3 receptor antagonists in the prophylaxis of acute nausea and vomiting when given according to guidelines in the first cycle of MEC*.

MASCC level of confidence: HighMASCC level of consensus: High

ASCO level of evidence: IASCO grade of recommendation: A

* Participants felt that the comparative data with palonosetron were interesting, but indicated that studies with this agent which follow guidelines (given with dexamethasone) are needed to change this guideline.

Multinational Association of Supportive Care in Cancer June 2004

June 2004

ANTIEMETIC TREATMENT GUIDELINESCommittee I: Emetic Risk Groups – Low risk

Single IV agents PaclitaxelDocetaxelMitoxantroneTopotecanEtoposidePemetrexedMethotrexateMitomycinGemcitabineCytarabine < 100 mg/m25-FluorouracilBortezomibCetuximabTrastuzumab

Single oral agents Capecetabine

June 2004

COMMITTEE VI (1/2):

Guideline for prevention of acute nausea and vomiting in patients receiving low risk emetic agents*:

A single agent (such as a low dose of a corticosteroid) is suggested for patients receiving agents of low emetic risk.

MASCC: Level of confidence: No confidence possible.MASCC: Level of consensus: moderate

ASCO level of evidence: III, IVASCO grade of recommendation: D

* While unusual at this emetic level, if a patient experiences emesis after guideline recommended therapy,it is advised that with subsequent treatment the regimen for the next higher emetic level should be given.

Multinational Association of Supportive Care in Cancer June 2004

June 2004

ANTIEMETIC TREATMENT GUIDELINESCommittee I: Emetic Risk Groups – Minimal Risk

BleomycinBusulfan2-ChlorodeoxyadenosineFludarabineVinblastineVincristineVinorelbineBevacizumab

ChlorambucilHydroxyureaL-Phenylalanine mustard6-ThioguanineMethotrexateGefitinib

Single oral agents

Single IV agents

June 2004

COMMITTEE VI (2/2):

Guideline for prevention of acute nausea and vomiting in patients receiving minimal risk antineoplastic agents*:

No antiemetic should be routinely administered beforechemotherapy in patients without a history of nauseaand vomiting.

MASCC level of confidence: no confidence possibleMASCC level of consensus: high

ASCO level of evidence: V and expert consensusASCO grade of recommendation: D

* While unusual at this emetic level, if a patient experiences emesis after guideline recommended therapy,it is advised that with subsequent treatment the regimen for the next higher emetic level should be given.

Multinational Association of Supportive Care in Cancer June 2004

June 2004

RECOMMENDED DOSES

OF ANTIEMETICS

June 2004

Recommended Doses of Serotonin Receptor(5-HT3) Antagonists for Acute Emesis

0.25 mgIVPalonosetron5 mgOral5 mgIVTropisetron

100 mgOral100 mg or 1.8 mg / KgIVDolasetron

2 mg (or 1 mg**)Oral1 mg or 0.01 mg / KgIVGranisetron

16 mg*Oral8 mg or 0.15 mg / KgIVOndansetron

DOSEROUTEAGENT

* Randomized studies have tested the 8 mg twice daily schedule** The 1 mg dose preferred by some panelists: small randomized study in MEC, Phase II study in HEC

Multinational Association of Supportive Care in Cancer June 2004

June 2004

Recommended Dexamethasone and Aprepitant Dosing

- Acute Emesis

- Delayed Emesis

- Acute Emesis

- Delayed Emesis

- Acute Emesis

80 mg orally, once for 2 days- Delayed Emesis

125 mg orally, once- Acute Emesis

Dose and ScheduleAPREPITANT

4 - 8 mg onceLow Risk

8 mg daily for 2 - 3 days(many panelists give the dose as 4 mg bid)

8 mg onceModerate Risk

8 mg bid for 3 - 4 days

20 mg onceHigh Risk

Dose and ScheduleDEXAMETHASONE

Multinational Association of Supportive Care in Cancer June 2004

June 2004

MULTIPLE CYCLES

June 2004

Addressing “AC”* as a Separate GroupGroups II - V

Although not part of the official recommendations for acute emesis in MEC, the panel agreed that it should be recognized that women receiving a combination of anthracycline plus cyclophosphamide represents a situation with a particularly great risk of nausea and vomiting.Additionally, it appears that the risk of nausea and vomiting increases during multiple cycles.

* AC = Anthracycline + Cyclophosphamide, includes regimens such as: AC, EC, FAC,and FEC. A = doxorubicin, E = epirubicin, C = cyclophosphamide, F = 5-FU.

Multinational Association of Supportive Care in Cancer June 2004

June 2004

June 2004

0

20

40

60

80

100

1. Cyc

le3.

Cycle

5. Cyc

le7.

Cycle

9. Cyc

le

Ondansetronplusmetopimazine

Ondansetronplusmetopimazineplusprednisolone

Cumulative complete protection rates in patients receivingCMF/CEF and antiemetic prophylaxis with ondansetron (OND)

prednisolone plus metopimazine (MPZ) or OND plus MPZ (n=220, 1462 courses of chemotherapy)

P = 0.0014

Sigsgaard et al. J Clin Oncol 2001;2091-7.

June 2004

Ongoing process to address emerging evidence in the future:

• Committees are permanent• Each chair queries the committee every 6 months regarding

whether there is new information which may affect the guideline• A steering committee queries the chairs for these suggestions• If evidence appears compelling, all group members are notified

for their opinions• If consensus is achieved, the Web-Guideline document

(MASCC) is updated. All participating Societies are notified.• Future print publications will have to be addressed – this should

be done in a coordinated way among the Societies

Keeping the Guidelines Accurate, Up-to-Date, and Valid -Keeping the Guidelines Accurate, Up-to-Date, and Valid -

PERUGIA 2004 ANTIEMETIC GUIDELINES- Process for the future:

PERUGIA 2004 ANTIEMETIC GUIDELINES- Process for the future:

Multinational Association of Supportive Care in Cancer June 2004

June 2004

Is there new information which may affect the guideline on acute nausea and vomiting?

• Does the addition of aprepitant improve the effect ofrecommended antiemetic therapy in patients receivingMEC? A-27

• Will randomized comparisons of palonosetron plus dexamethasone (+/- aprepitant) versus other 5-HT3receptor antagonists plus dexamethasone (+/- aprepitant) affect the guideline?


Top Related