Hot and Bothered FEBRILE NEUTROPENIA. Dr. Mark Kristjanson. Community Cancer Care 215 Educational Conference

Transcription

1 Hot and Bothered FEBRILE NEUTROPENIA Dr. Mark Kristjanson Community Cancer Care 215 Educational Conference

2 Presenter Disclosure Faculty: Mark Kristjanson MD, CCFP Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: Casey Hein & Associates Consulting Fees: Casey Hein & Associates (to review educational materials on topic of Oral-Systemic Health) Other: member of Cancer Patient Journey Initiative s PCWG

3 Mitigating Potential Bias No potential bias identified.

4 Learning Objectives By the end of the session, the learner will be able to: Explain the pathophysiology of febrile neutropenia; Describe how risk assessment of patients with FN is done; Give examples of initial empiric antibiotic regimens for high risk and low risk febrile neutropenic events; Apply the recommendations of CCMB s new policy on the use of filgrastim in the management of patients on chemotherapy.

5 Neutropenia Neutropenia, severe: ANC of <500 cells/mm3 or predicted decline in next 48H to <500 cells/mm 3 Neutropenia, profound: ANC <100 cells/mm3 Fever: a single oral temperature (T) 38.3ºC or > 38ºC (100.4ºF) for one hour or >38ºC (100.4ºF) at least twice over 12 hours CCMB Neutropaenia Protocol February 6th, 2012

6 SIRS: Systemic Inflammatory Response The presence of 2 of the following: Body temperature of > 38 C or < 36 C; Heart rate > 90 bpm; RR > 20/min or PaCO 2 of < 32 mmhg; WBC > 12 x 10 9 /L or < 4.0 x 10 9 /L or > 10% bands

7 More Definitions Sepsis Syndrome The term sepsis is defined as SIRS that is as a result of a confirmed infectious process Severe Sepsis Syndrome Sepsis syndrome + hypotension or hypoperfusion (e.g. lactic cidosis, oliguria, or confusion) Septic Shock Sepsis-induced hypotension despite adequate fluid resuscitation + evidence of hypoperfusion.

8 FNE: Pathophysiology

9 FNE: Pathophysiology

10 van Vliet MJ, Harmsen HJ, de Bont ES, Tissing WJ. The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS pathogens 2010; 6(5): e

11 Infection in Febrile Neutropenia Patients Profile for Low-risk Solid Tumour Patients Cytotoxic therapy Mean absolute neutrophil count ( x 10 9 /L) Empirical antibacterial therapy Temperature ( C) Chemotherapy Day Bow E.J. Semin Hematol 2009, 46(3):

12 Fever and Infection in Neutropaenic Cancer Patients The 1 st Fever Profile: High Risk Cytotoxic therapy Absolute neutrophil count ( x 10 9 / L ) Induction Consolidation Day +12 FNE Empirical anti-bacterial therapy Defervescence Day +16 FNE d +5 Haematopoietic growth factor effect Chemotherapy Day Temperature ( C) Bow E.J. Semin Hematol 2009, 46(3):

13 Filgrastim Natural G-CSF is 175 amino acid glycoprotein produced by monocytes, fibroblasts, endothelial cells Binds to hematopoetic cell surface receptors Stimulates production by the marrow of neutrophils Recombinant Granulocyte Colony Stimulating Factor (G-CSF)+ N-terminal methionine = Filgrastim Elimination half life of 3.5 H

14 Primary Prophylaxis with CSFs: CCMB Recommended for prevention of FN if Chemotherapy regimens associated with > 20% FN risk; In the setting of adjuvant treatment with curative intent. Required for dose dense regimens Also consider if 3 or more major co-morbidities Age > 70 counts as a major risk factor Never primary prophylaxis for metastatic/palliative regimens

15 Secondary Prophylaxis Curative* intent /adjuvant regimens AND febrile neutropenia (or prolonged neutropenia) with previous cycle AND dose reductions likely to compromise outcomes E.g. to maintain dose density if FNE on a previous cycle (or if prolonged neutropenia without fever caused dose delay) for 1. FEC for breast 2. Small cell lung Ca (Any request for filgrastim for use in a Thoracic regimen will require non-formulary approval.) *Exception: to maintain FOLFIRINOX in metastatic pancreatic cancer if 2 (two) previous dose reductions

16 Filgrastim: Dose Reduce or Delay? If febrile neutropenic event occurs, delay the next cycle AND reduce the dose for any curative/adjuvant regimen for which dose reduction dose not compromise outcomes e.g FOLFOX in colorectal cancer And for any metastatic regimen (see FOLFIRINOX caveat)

17 Filgrastim: Dose reduce or delay If counts are too low to safely proceed with next chemo cycle ALWAYS delay, and DON T use filgrastim late in the cycle to rescue the counts

18 PEG-filgrastim Filgrastim attached to polyethylene glycol Half life of hours More expensive Cost effective to use instead of 10 days of filgrastim

19 PEG-filgrastim Example: a patient gets prolonged neutropenia after first cycle of FEC; so you delay cycle 2 and added filgrastim for five days; and they got FNE with cycle 2 so you delay (not reduce) the dose again; and gave a 7 day course of filgrastim with cycle 3, which worked well; but now you expect 10 days of filgrastim will be needed with docetaxel; so give PEG-filgrastim.

20 CCMB and filgrastim: Breast Primary prophylaxis is not mandatory but can be considered for the docetaxel component of FEC-D FEC does not typically require primary prophylaxis, although an elderly patient with multiple major comorbidities could be considered for primary prophylaxis, in consultation with the attending oncologist; For the FEC component of FEC-D, secondary prophylaxis should be used, in order to maintain dose density in those patients who experience FN or who have a cycle delayed on account of prolonged neutropenia in a previous cycle.

21 CCMB and filgrastim: GI 1. There are no Gastrointestinal Disease Site Group regimens that require primary prophylaxis with filgrastim. 2. Secondary prophylaxis with filgrastim is only recommended for patients treated with FOLFIRINOX only AFTER two dose reductions has been given.

22 CCMB & filgrastim: Lymphoma 1. Routine use of filgrastim in ABVD protocol for Hodgkin lymphoma is not recommended. The use of filgrastim can be considered in patients who have developed a febrile neutropenic event while on ABVD. 2. Bendamustine-based chemotherapy regimens do not require filgrastim. The recommendation is to dose reduce bendamustine. 3. All patients who receive Dose-Adjusted R-EPOCH are eligible to receive filgrastim as it is incorporated into this regimen. Peg-filgrastim is not an option in the Dose- Adjusted R-EPOCH protocol as the dose adjustments are studied with filgrastim only. 4. Route use of filgrastim with R-CVP is not recommended.

23 CCMB & filgrastim: Lymphoma 5. GDP (+/-R): The use of filgrastim as secondary prophylaxis is permitted for patients who develop a febrile neutropenic event and are treated with curative intent. If neutropenia was an issue during first line therapy, then filgrastim should be made available for primary prophylaxis to patients receiving GDP with the caveat that they are treated with curative intent. 6. The Disease Site Group does not recommend routine use of filgrastim in all patients treated with R-CHOP. The use of primary prophylaxis can be considered in patients who are over 65 years of age OR in younger patients with HIV and other immunosuppressive disorders (i.e. due to chronic methotrexate). Patients are eligible for filgrastim as secondary prophylaxis if R-CHOP is used with curative intent.

24 CCMB & filgrastim: Lymphoma 7. Primary prophylaxis is recommended with the following regimens: ESHAP, ICE or DHAP. 8. All usage of growth factor support for myeloma regimens will require approval via a non-formulary request with justification. 9. All usage of growth factor support for chronic lymphocytic leukemia regimens will require approval on a case-by-case basis via a non-formulary request with justification. Usage of filgrastim is not recommended with fludarabine-based regimens.

25 Filgrastim Not for the management of acute febrile neutropenia Exception: septic shock; ICU admission

26 MASCC Score (maximum = 26)

27 FNE: Low Risk MASSC score > or = 21 Neutropenic nadir not expected to be profound / prolonged No high risk infectious disease locus ( e.g. pneumonia, meningitis) that mandates initial IV treatment Not in shock

28 FNE: Initial Antimicrobial Therapy Low risk oral fluoroquinolone* (levofloxacin 750 mg od or ciprofloxacin 750 mg BID plus amoxicillin/clavulanate** (500/125 TID) Contact by telephone within 24 hours Clinic visit within hours, and every 2nd day until defervescence and myeloid reconstitution *unless given as primary prophylaxis ** if penicillin allergic give clindamycin

29 FNE: High Risk MASCC score 20 or lower And/or patient shocky And/or neutropenic nadir expected to be profound/ prolonged And/or type of infection warrants initial IV antibiotic (pneumonia, meningitis, MRSA suspected, etc)

30 FNE: Initial Antimicrobial Therapy High risk hospitalize for IV initial empirical antibiotic therapy monotherapy with anti-pseudomonal β-lactam agent, such as cefepime, a carbapenem, or piperacillin-tazobactam Piperacillin/tazobactam 4.5 grams IV Q 8 hours (CCMB)

31 The End Thank you!