Upload
others
View
5
Download
0
Embed Size (px)
Citation preview
© 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 Ondansetron 32 mg withdrawn in 2012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