© 2010 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.

ANTIEMETICSand

FEBRILE NEUTROPENIA

ANTIEMETICSand

FEBRILE NEUTROPENIA

Matti S. Aapro

Genolier

Switzerland

22

Disclosures

Collaborations in this field:

•Teva, Sanofi, Sandoz, Roche, Novartis, Merck, Johnson & Johnson, Hospira, Helsinn, Amgen

CLINIQUE DE GENOLIER

Take Home Message

“Supportive care makes excellent cancer care

possible”

Dorothy M.K. Keefe,

MASCC immediate past-president

Effective CINV Management

…in the Elderly Patient

Specific issues in elderly patients

SDU University of Southern Denmark

OUH Odense University Hospital

Prevention of Nausea and Vomiting

Jørn Herrstedt MD

Professor, Dr. Med.

Antiemetic Guidelines have no Specific Age-Related Recommendations!

Patient-Related Risk Factors

• Organ function

• Absorption and distribution

• Liver

• Kidney

• Bone marrow

• Comorbidity

• Polypharmacy

• Dehydration and/or electrolyte disturbances

• Compliance

Age-Related Risk Factors CINV

Cardiovascular Issues in Old Generation 5-HT3RAs

• In December 2010, FDA advised that Anzemet injection (dolasetron mesylate) should no longer be used to prevent CINV in pediatric and adult patients due to new data demonstrating its ability to increase the risk of torsades de pointes.

• Based on Kytril (granisetron hydrochloride) SPC section 5,2: : “QT prolongation has been reported with KYTRIL. Use with caution in patients with pre-existing arrhythmias or cardiac conduction disorders.

• 9-15-11 FDA safety announcement : “Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm”. Ondansetron 32 mg withdrawn in 2012

© 2010 Multinational Association of Supportive Care in CancerTM All rights reserved worldwide.

MASCC/ESMO Antiemetic Guideline 2010UPDATED ONLINE in 2013

Multinational Associationof Supportive Care in Cancer

Organizing and Overall Meeting Chairs:Richard J. Gralla, MD

Fausto Roila, MD

Maurizio Tonato, MD

Jørn Herrstedt, MD

MASCC/ESMO Antiemetic GuidelineSummary of Acute and Delayed Prevention

* If a NK-1 RA is not available then palonosetron is the preferred

5-HT3 RA also in AC regimensAdapted from reference 3 nd www.mascc.org

Emetic risk group

Risk (% pts)

Acute prevention Delayed prevention

High >90%5-HT3 RA

+ DEX + (fos)aprepitant DEX + aprepitant

AC combinations -5-HT3 RA *

+ DEX + (fos)aprepitant aprepitant

Moderate 30-90% Palonosetron + DEX DEX

Low 10-30% single agent (DEX, 5-HT3 DRA) No routine prophylaxis

Minimal <10% No routine prophylaxis No routine prophylaxis

Recommended 5-HT3 RAs: Palo, Grani, Onda, Dola oral, TropiDEX, dexamethasone; AC, anthracycline-cyclophosphamide DRA: dopamine receptor antagonistAprepitant in delayed phase depends on (fos)apretitant use in acute phase

• Adhere to guidelines

• Careful assessment of:

• The cancer and its impact

• Organ function

• Polymorbidity

• Polypharmacy

• Compliance

• Keep it simple

• Close follow-up

CONCLUSION…of course I agree with Prof Herrstedt

Emesis and Cancer Treatment

Approach to the Problem

In controlling emesis,

the strategy is prevention

rather than

treatment

1. Gralla RJ, Osoba D, Kris MG et al. Recommendations for the use of antiemetics: Evidence-

based, clinical practice guidelines. J Clin Oncol 1999;17(9):2971–2994.

Radiotheray-induced Emesis (RINV)

Group Irradiated Area Recommendation

MASCC

ASCO

NCCN

1. Prophylaxis or rescue. 2. Rescue only.

5-HT3-RA = serotonin3-receptor antagonist. DEX = dexamethasone

TBI 5-HT3-RA + DEX

Upper abdomen 5-HT3-RA +/- DEX

Lower thorax, pelvis, H&N 5-HT3-RA1

Breast, extremities 5-HT3-RA2 or DOPA-RA 2

TBI and upper abdomen See MASCC

Lower thorax 5-HT3-RA

Head & neck, breast etc. Rescue, see MASCC

TBI and upper abdomen See MASCC

Other sites Rescue

PREVENTION

AND

MANAGEMENT OF

FEBRILE NEUTROPENIA

17

Myeloid growth factors for chemotherapy associated neutropenia

Kuderer NM, et al. Cancer 2006;106:2258–66

Chirivella I, et al. J Clin Oncol 2006;24:668

Bosly A, et al. Ann Hematol 2008;87:277–83

Myelosuppressive chemotherapy

Febrile neutropenia (FN) Chemotherapy dose delays and dose reductions

Decreased relative dose intensity (RDI)

Complicated life-threatening infection and

prolonged hospitalization

Neutropenia

Reduced survival

18

Chemotherapy with G-CSF supportRelative risk for all-cause mortality and relative dose intensity

Lyman GH et al. J Clin Oncol 2010;28:2914-24

19

Guidelines for Myeloid Growth Factor Support

European Organisation for Research and Treatment

of Cancer (EORTC)1

American Society of Clinical Oncology (ASCO)2

National Comprehensive Cancer Network (NCCN)3

European Society for Medical Oncology (ESMO)4

1Aapro et al. Eur J Cancer 2011;47:8–32; 2Smith et al. J Clin Oncol 2006;24:3187–205; 3National Comprehensive Cancer Network 2011;http://www.nccn.org/professionals/physician_gls/pdf/myeloid_growth.pdf 4Crawford et al. Annals of Oncology 2010;21(Suppl 5):v248–51;.

21

WHAT TO DO IF FN HITS:

PATIENT EVALUATION

AND EMPIRICAL ANTIBIOTICS

Prof. Jean KLASTERSKY

Jules Bordet Institute

Université Libre de Bruxelles

Brussels - Belgium

22

Klastersky, Jean. (2013). Febrile Neutropenia. London: Springer Healthcare

23Klastersky, Jean. (2013). Febrile Neutropenia. London: Springer Healthcare

A MASCC score index ≥ 21 predicts a risk of

complications < 5%

25

EORTC Trial XV

Low risk patients (530 episodes)

• MASCC > 21

• other restrictive criteria

• able to take oral medications

Double blind randomization

Moxifloxacin

(once daily)

Ciprofloxacin

Amoxycilline clavulanate

Outpatient management

• no serious comorbidity

• home environnment OK

• compliance and consent OK J. Clin. Oncol., 2013

Success: 80%Survival: 99%

Success: 82%Survival: 99%

IDSA 2010 Guidelines

Freifeld et al, Clin Infect Dis 2011

27

Independent risk factors of serious complications by multivariable logistic regression analysis

Independent risk factors

ImportanceNormalized importance

Latency of the first dose

of antibiotics0.072 1.000

Pneumonia 0.063 0.877

Platelet count ≤

50,000/µl0.043 0.598

Comorbidity 0.022 0.308

Pulse rate ≤ 100

beat/min0.021 0.287

Hematol Oncol 2013, J-J Lynn et al.

28

TAKE-HOME MESSAGES

If FN hits

•Evaluate the risk of complications (MASCC score)

•Start antibiotics early (within 1 hour)

•For low risk: observe 12 to 24 hours before sending back home

•For non-low risk: evaluate for severe sepsis / septic shock and consider

ICU

•Monotherapy is adequate in most cases

(! But consider local microbiologic epidemiology)

•Critically re-evaluate after 48 hours

SUPPORTIVE CARE IN CANCER

28th International Symposium

MASCC/ISOO

AVEC SÉANCE AFSOS

June 2015, Copenhagen, DenmarkJune 2015, Copenhagen, Denmark

www.mascc.org

DECEMBER 5: A JOINT MASCC SIOG SESSION

Chairs: D. Keefe (AUS) ; G. Zulian (CH)

…Bone health: a key factor in elderly and not so elderly patients with

cancer M. Aapro (CH)

…Mucositis and new drugs: to prevent or to treat? D. Keefe (AUS)

…Depression: an issue in survivorship for elderly cancer patients. L.

Balducci (USA)

…Ovarian cancer: issues in the long term for elderly patients C. Steer (AUS)

Thank you foryour kind attention

See you later !

33