Download ANTIEMETICS and FEBRILE NEUTROPENIA Matti S. Aapro

ANTIEMETICS
and
FEBRILE NEUTROPENIA
Matti S. Aapro
Genolier
Switzerland
© 2010 Multinational Association of Supportive Care in CancerTM
All rights reserved worldwide.
Disclosures
Collaborations in this field:
•Teva, Sanofi, Sandoz, Roche,
Novartis, Merck, Johnson & Johnson,
Hospira, Helsinn, Amgen
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CLINIQUE DE GENOLIER
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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
Prevention of Nausea and Vomiting
Jørn Herrstedt MD
Professor, Dr. Med.
SDU
University of Southern Denmark
OUH
Odense University Hospital
Antiemetic Guidelines have no
Specific Age-Related
Recommendations!
Patient-Related Risk Factors
Age-Related Risk Factors CINV
• Organ function
• Absorption and distribution
• Liver
• Kidney
• Bone marrow
• Comorbidity
• Polypharmacy
• Dehydration and/or electrolyte disturbances
• Compliance
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 Ondansetron 32 mg withdrawn in 2012
MASCC/ESMO Antiemetic Guideline 2010
UPDATED ONLINE in 2013
Multinational Association
of Supportive Care in Cancer
Organizing and Overall Meeting Chairs:
Richard J. Gralla, MD
Fausto Roila, MD
Maurizio Tonato, MD
Jørn Herrstedt, MD
© 2010 Multinational Association of Supportive Care in CancerTM
All rights reserved worldwide.
MASCC/ESMO Antiemetic Guideline
Summary of Acute and Delayed Prevention
Emetic
risk group
Risk
(% pts)
Acute prevention
Delayed prevention
>90%
5-HT3 RA
+ DEX + (fos)aprepitant
DEX + aprepitant
-
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
<10%
No routine prophylaxis
No routine prophylaxis
High
AC combinations
Minimal
Recommended 5-HT3 RAs: Palo, Grani, Onda, Dola oral, Tropi
DEX, dexamethasone; AC, anthracycline-cyclophosphamide DRA: dopamine receptor antagonist
Aprepitant in delayed phase depends on (fos)apretitant use in acute phase
* If a NK-1 RA is not available then palonosetron is the preferred
5-HT3 RA also in AC regimens
Adapted from reference 3 nd www.mascc.org
CONCLUSION…
of course I agree with Prof Herrstedt
• Adhere to guidelines
• Careful assessment of:
• The cancer and its impact
• Organ function
• Polymorbidity
• Polypharmacy
• Compliance
• Keep it simple
• Close follow-up
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: Evidencebased, clinical practice guidelines. J Clin Oncol 1999;17(9):2971–2994.
Radiotheray-induced Emesis (RINV)
Group
MASCC
ASCO
Irradiated Area
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.
NCCN
Recommendation
Rescue, see MASCC
TBI and upper abdomen
See MASCC
Other sites
Rescue
1. Prophylaxis or rescue.
2. Rescue only.
5-HT3-RA = serotonin3-receptor antagonist. DEX = dexamethasone
PREVENTION
AND
MANAGEMENT OF
FEBRILE NEUTROPENIA
Myeloid growth factors for chemotherapy
associated neutropenia
Myelosuppressive chemotherapy
Neutropenia
Febrile neutropenia (FN)
Chemotherapy dose delays
and dose reductions
Complicated lifethreatening infection and
prolonged hospitalization
Decreased relative dose
intensity (RDI)
Reduced survival
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
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Chemotherapy with G-CSF support
Relative risk for all-cause mortality and relative dose intensity
Lyman GH et al. J Clin Oncol 2010;28:2914-24
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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;.
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WHAT TO DO IF FN HITS:
PATIENT EVALUATION
AND EMPIRICAL ANTIBIOTICS
Prof. Jean KLASTERSKY
Jules Bordet Institute
Université Libre de Bruxelles
Brussels - Belgium
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Klastersky, Jean. (2013). Febrile Neutropenia. London: Springer Healthcare
Klastersky, Jean. (2013). Febrile Neutropenia. London: Springer Healthcare
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A MASCC score index ≥ 21
predicts a risk of
complications < 5%
EORTC Trial XV
Low risk patients (530 episodes)
• MASCC > 21
• other restrictive criteria
• able to take oral medications
Double blind randomization
Moxifloxacin
Ciprofloxacin
(once daily)
Amoxycilline clavulanate
Success: 80%
Survival: 99%
Outpatient management
• no serious comorbidity
• home environnment OK
• compliance and consent OK
Success: 82%
Survival: 99%
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J. Clin. Oncol., 2013
IDSA 2010 Guidelines
Freifeld et al, Clin Infect Dis 2011
Independent risk factors of serious complications by multivariable
logistic regression analysis
Independent
risk factors
Importance
Normalized
importance
Latency of the first dose
of antibiotics
0.072
1.000
Pneumonia
0.063
0.877
Platelet count ≤
50,000/µl
0.043
0.598
Comorbidity
0.022
0.308
Pulse rate ≤ 100
beat/min
0.021
0.287
Hematol Oncol 2013, J-J Lynn et al.
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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
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SUPPORTIVE CARE IN CANCER
28th International Symposium
MASCC/ISOO
AVEC SÉANCE AFSOS
June 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 for
your kind attention
See you later !
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