טיפול בגורמי צמיחה של השורה הלבנה: קווים מנחים בספרות ו...
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טיפול בגורמי צמיחה של השורה הלבנה: קווים מנחים בספרות ונתונים לביסוסם - מפגש החוג לכימותרפיה/האיגוד הישראלי לרדיותרפיה ואונקולוגיה קליני- שרתון סיטי טאור 19.5.06 (עודכן- דצמבר 2008) פרופ' נסים חיים - מכון אונקולוגי-מ.ר. רמב"ם. CSFs. Therapeutic benefits…. Side effects…. Guidelines….

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Csfs

טיפול בגורמי צמיחה של השורה הלבנה: קווים מנחים בספרות ונתונים לביסוסם - מפגש החוג לכימותרפיה/האיגוד הישראלי לרדיותרפיה ואונקולוגיה קליני- שרתון סיטי טאור19.5.06

(עודכן- דצמבר 2008)

פרופ'נסים חיים - מכון אונקולוגי-מ.ר. רמב"ם


Csfs

CSFs

  • Therapeutic benefits….

  • Side effects….

  • Guidelines….


Therapeutic benefits of csfs

Therapeutic benefits of CSFs

Reduces the risk of febrile neutropenia?


Reduced risk of febrile neutropenia

Reduced risk of febrile neutropenia

“Administration of CSFs result in a 50% risk reduction of developing febrile neutropenia”(NCCN Practice Guidelines in Oncology – v.2.2005 (Overview).


Csfs

1.0

0.8

G-CSF

0.6

Proportion Free of Fever with Neutropenia

0.4

Placebo

0.2

0.0

0

1

2

3

4

5

6

Cycles of Chemotherapy

Chemotherapy Induced Neutropenia

Planned DI + G-CSF

Primary prophylaxis

Crawford J. et al. N Engl J Med 1991;325:164-170.

Purpose:

Testing the hypothesis and clinical implications of chemotherapy-related neutropenia reduction in patients with cancer.

Patients and methods:

211 SCLC patients participated a double-blind, randomized, placebo-controlled trial of G-CSF support to 6 cycles of Cyclophosphamide, Doxorubicin, and Etoposide.

P < 0.001


Risk of febrile neutropenia with and without gcsf results of a meta analysis

39.5%

22.4%

GCSF

Control

Risk of febrile neutropenia with and without GCSF-results of a meta-analysis

Kuderer NM et al. J Clin Oncol 25: 3158-67, 2007(a meta-analysis of 15 controlled trials (n=3182 pts) using GCSF before the onset of fever or neutropenia following systemic chemotherapy for solid tumors or lymphomas):

Mean risk for FN

RR=0.54---P<,0001


Therapeutic benefit of csfs

Therapeutic benefit of CSFs

Shortens the length of neutropenia and febrile neutropenic episode, and reduces the period of hospitalization and IV antibiotics?


Csfs

100

10

Placebo

1

Neutrophils X 109/L

G-CSF

0.1

0.01

0

3

6

9

12

15

18

21

Day of Treatment

(CDE – Cyclophosphamide, Doxorubicin, Etoposide)

Trillet-Lenoir V. et al. Eur J Cancer 1993;29A(3):319-324.


Csfs

Neupogen reduces the duration of hospitalizationand i.v. antibiotic use in patients with AML

p=0.0001

30

20

10

0

p=0.0001

Median duration (days)

Hospitalisation i.v. antibiotics

Neupogen

Placebo

Adapted from Heil G et al. Blood 1997


Therapeutic benefit of csfs1

Therapeutic benefit of CSFs

Reduces the risk of documented infection?


Risk of documented infection results of a meta analysis

mean risk of documented infection

Risk of documented infection-results of a meta-analysis

Lyman GH et al. Am J Med 112: 406-11, 2002(a meta-analysis of 8 controlled trials (n=1144 pts)…7 trials reported information on the documented infection…

Odds ratio= 0.51 (p= 0.001)


Therapeutic benefit of csfs2

Therapeutic benefit of CSFs

Reduces the risk of documented infection-related mortality?


Risk of documented infection related mortality results of a meta analysis

2.8%

1.5%

Control

GCSF

Risk of documented infection-related mortality- results of a meta-analysis

Kuderer NM et al. J Clin Oncol 25: 3158-67, 2007(a meta-analysis of 12 controlled trials (n=3122 pts) using GCSF before the onset of fever or neutropenia following systemic chemotherapy for solid tumors or lymphomas):

(RR=0.55; P=0.018)

*reduction in infection-related mortality was significant among studies of filgrastim but did not reach statistical significance with lenograstim or pegfilgrastim.


Csfs

Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection(Sung L et al. Ann Intern Med 147:400-11, 2007)

  • BACKGROUND: Benefits of prophylactic hematopoietic colony-stimulating factors (CSFs) in adults and children receiving cancer chemotherapy or undergoing stem-cell transplantation (SCT) are unclear. PURPOSE: To determine whether prophylactic CSFs decrease mortality, infections, and febrile neutropenia more than does placebo or no therapy in patients with cancer and in patients undergoing SCT. DATA SOURCES: Electronic searches of Ovid MEDLINE and EMBASE from inception until April 2007 and of the Cochrane Central Register of Controlled Trials until the second quarter of 2006. STUDY SELECTION: We selected 148 trials that were reported in any language that randomly assigned patients to CSFs or to either placebo or no therapy. Prophylactic CSFs were given concurrently with or after initiation of chemotherapy. DATA EXTRACTION: Two reviewers independently extracted data onto standardized forms. DATA SYNTHESIS: Short-term all-cause mortality appeared to be similar between the prophylactic CSF and the control groups (7.6% vs. 8.0%; relative risk, 0.95 [95% CI, 0.84 to 1.08]; absolute risk reduction, 0.4% [CI, -0.5% to 1.4%]). Risks for infection-related death with CSFs and placebo or no therapy were 3.1% and 3.8%, respectively (relative risk, 0.82 [CI, 0.66 to 1.02]; absolute risk reduction, 0.8% [CI, 0.0% to 1.5%]). Use of CSFs reduced the following more than did placebo or no therapy: documented infections (median rate, 38.9% vs. 43.1%; rate ratio, 0.85 [CI, 0.79 to 0.92]), microbiologically documented infections (median rate, 23.5% vs. 28.6%; rate ratio, 0.86 [CI, 0.77 to 0.96]), and episodes of febrile neutropenia (median rate, 25.3% vs. 44.2%; rate ratio, 0.71 [CI, 0.63 to 0.80]). LIMITATIONS: Trial designs, including assessments of infections, and participants were heterogeneous. Estimates of mortality effects were imprecise. CONCLUSIONS: Prophylactic CSFs may have little or no effect on mortality but do decrease rates of infection in patients receiving cancer chemotherapy or those undergoing SCT.


Therapeutic benefit of csfs3

Therapeutic benefit of CSFs

Reduces the need for dose reductions and treatment delays (& reduced dose-intensity)?


Relative dose intensity rdi

Mean RDI

95.1%

86.7%

Controls

GCSF

Relative Dose Intensity (RDI)

Kuderer NM et al. J Clin Oncol 25: 3158-67, 2007(a meta-analysis of 10 controlled trials using GCSF before the onset of fever or neutropenia following systemic chemotherapy for solid tumors or lymphomas):

P = 0.001


Therapeutic benefit of csfs4

Therapeutic benefit of CSFs

Enables full-dose following a prior cycle with febrile neutropenia?


Full dose chemotherapy following a prior cycle with febrile neutropenia

Full-dose chemotherapy following a prior cycle with febrile neutropenia

  • Metastatic small cell lung cancer treated with a combination of cyclophosphamide, doxorubicin, and etoposide

  • Patients who developed neutropenic fever during the first cycle received the second cycle with full dose+ G-CSF

  • Only 23% of these patients developed neutropenic fever during the second cycle.

    (Crawford J et al. N Engl J Med 1991; 325: 164-170)


Csfs

Full-dose chemotherapy with GCS-F support* following a prior cycle with febrile neutropenia- Dept Oncology, Rambam Medical Center experience

  • Since September 1995, a standard policy in patients treated with an intent for cure or for durable complete remission.

    * filgrastim (neupogen)300 or 480 mcg/day for ~10 days


Eligibility criteria

Eligibility Criteria

  • Neutropenic fever was not associated with life-threatening infection.

  • There were no other dose-limiting toxicities.

  • Age 75 or less; performance status (WHO) 0-2


Diagnosis in 51 patients who developed neutropenic fever without gcsf age 22 75 median 47

Diagnosis in 51 patients who developed neutropenic fever (without GCSF)—(age:22-75,median: 47)


Chemotherapy protocols n 51

Chemotherapy protocols (n=51)


Next cycle n 1 full dose with gcsf support in all pts

Next cycle (n+1) (full dose with GCSF support in all pts)

  • Number of pts…………………………………………51

  • Neutropenic fever:……………………..8/51(16%)

  • Days of IV antibiotics:…..4.5 (median),(3-7)

  • Evidence of bacterial infection:…………none


Next cycle n 2 full dose with gcsf support in all pts

Next cycle (n+2) (full dose with GCSF support in all pts)

  • Number of pts…………………………………………41

  • Neutropenic fever:……………………..4/41 (10%)

  • There was no drug-related death associated with either cycle.


Csfs

A policy of full-dose chemotherapy with secondary G-CSF support in pts who develop febrile neutropenia following moderately myelotoxic chemotherapy is relatively safe and feasible.

Haim N, Shulman K, Goldberg H, Tsalic M. Med Oncol 22: 229-32, 2005


Therapeutic benefit of csfs5

Therapeutic benefit of CSFs

Enables administration of dose-dense therapy?


Dose intensity dose density

Dose-intensity & Dose-density

90 mg/m2 every 3 wks vs.

30 mg/m2/week:

  • Both regimens have the same dose intensity.

  • 30 mg/m2/week gives a greater dose

    density than the 3-weekly administration.


Tolerability of dose dense chemotherapy with gcsf breast cancer

Tolerability of dose-dense chemotherapy with GCSF-breast cancer

Citron ML et al. J Clin Oncol 21: 1431-39, 2003

  • AC (doxorubicin 60 mg/m2 & cyclophosphamide 600 mg/m2)

    q 3 wks or q 2 weeks +filgrastim days 3-10 at 5 mcg/kg rounded to either 300 or 480 mcg.

  • Treatment was well tolerated. Severe neutropeniawas less frequent in patients who received the dose-dense regimens (6% vs. 33%).


Dose dense chop chop 14

Dose-dense CHOP (CHOP-14)

  • Cyclophosphamide 750 mg/m2 IV, day 1

  • Adriamycin 50 mg/m2 IV , day 1

  • Vincristine 1.4 mg/ m2 IV , day 1

  • Dexamethasone 20 mg IV, day 1

  • Prednisone 100 mg PO, days 2-5

  • Cycles are repeated every 2 weeks.

  • GCSF is given on days 4-13.

  • Pfreundschuh M et al. Blood 104: 626-33, 2004 (young pts)

  • Pfreundschuh M et al. Blood 104: 634-41, 2004 (elderly pts)


Therapeutic benefit of csfs6

Therapeutic benefit of CSFs

Enables administration of “high-dose” chemotherapy (without peripheral blood stem cell support)?


Chop mega chop in aggressive non hodgkin s lymphomas

CHOP & Mega CHOP in aggressive non Hodgkin`s lymphomas

CHOP:

  • Cyclophosphamide750 mg/m2 IV, day 1

  • Adriamycin 50 mg/m2 IV , day 1

  • Vincristine 1.4 mg/ m2 IV , day 1

  • Prednisone 100 mg PO, days 1-5

    (cycles repeated every 3 weeks)

    “Mega” CHOP:

  • Cyclophosphamide1500mg/m2 IV (1hr), days

  • 1 and 2

  • Mesna 200 mg/m2 X 4, IV, day 1; 200 mg/m2 X 8,IV day 2

  • Adriamycin 50 mg/m2 IV , day 1

  • Vincristine 1.4mg/m2 (max. 2mg) IV, day 1

  • Prednisone 100 mg PO , days 1-5

    (cycles repeated every 3 weeks)


Therapeutic benefit of csfs7

Therapeutic benefit of CSFs

Improves the outcome of febrile neutropenia when started at the time of established neutropenia?


Asco 2000 guidelines for gcsf therapy febrile patients with neutropenia 2000

ASCO 2000 Guidelines for GCSF Therapy- Febrile Patients with neutropenia (2000)

  • “The results of 8 randomized trials provide strong and consistent support for the recommendation that G-CSFs should not be routinely used as adjunct therapy for the treatment of uncomplicated fever and neutropenia…”.

  • GCSF should be considered in pts with complicated neutropenia and fever”.


Csfs

CSFs for chemotherapy-induced febrile neutropenia: a meta-analysis (Clark OAC et al. J Clin Oncol 23: 4198-4214, 2005)(13 trials with a total of 1,518 pts)

  • Significantly reduces the length of hospitalization(HR=0.63;P=0.006)

  • Significantly reduces the time to neutrophil recovery(HR=0.32;P<0.0001).

  • A marginally significant result was obtained for the use of CSF in reducing infection-related mortality(3.1% VS. 5.7%; HR=0.51; p=0.05).


Therapeutic benefit of csfs8

Therapeutic benefit of CSFs

Improves treatment outcome?


Csfs

ESMO recommendations for the application of haematopoietic growth factors (hGFs). Ann Oncol 12: 1219-20, 2001:

No high level evidence for increase in survival


Csfs in lymphoma meta analysis

CSFs in lymphoma-meta-analysis

Bohlius J et al. Cochrane Database Syst Rev. 3: CD003189, 2004 (12 eligible randomized controlled trials with 1823 pts):

  • -----reduced the risk of neutropenia, febrile neutropenia and infection.

  • However, there is no evidence that CSFs provide a significant advantage in terms of CR, freedom from treatment failure or overall survival.


Therapeutic benefit of csfs9

Therapeutic benefit of CSFs

Enables stem cell

mobilization ?


Csfs

Side effects


Adverse events bone pain

Adverse Events –“Bone pain”

  • In bone marrow bearing locations

  • Usually of mild/moderate severity ~(15%)*

  • Transient - controlled with oral analgesics

    *Med Oncol 22: 229-32, 2005: 20/51(=39%);severe in 8 (=16%)


Adverse events transient elevations in ldh uric acid and alkaline phosphatase

Adverse Events – Transient elevations in LDH, uric acid, and alkaline phosphatase

  • InLDH, and uric acid: attributed to the proliferative effects of G-CSF on neutrophil precursors in the bone marrow, with increased cell turnover

  • In alkaline phosphatase: potentially secondary effects on bone.


Gcsf and lung toxicity

GCSF and lung toxicity

Pulmonary complications of GCSF are very rare and include cough, dyspnea, and interstitial or alveolar pulmonary edema. Few cases of acute respiratory distress syndrome have been reported.


A possible interaction between bleomycin and gcsf

A possible interaction between bleomycin and GCSF

Martin WG et al. J Clin Oncol 23: 7614-20, 2005 :

GCSF was associated with increased lung toxicity in Hodgkin`s disease patients treated with bleomycin containing drug combinations).

(GCSF may enhance bleomycin-induced lung toxicity by a mechanism that probably involved neutrophils).

On the other hand:

Saxman SB et al. Chest 111: 657-60, 1997:

Fossa SD et al. J Clin Oncol 16: 716-24, 1998:

There is no increase in pulmonary toxicity with co-administration of G-CSF and bleomycin compared to bleomycin alone in pts with advanced germ cell tumors.


Gcsf effect on spleen

GCSF: effect on spleen

  • Spleen enlargement (Picardi M et al. Haematologica 88: 794, 2003),

  • Splenic rupture (Falzetti F et al. Lancet 353: 555, 1999; Dincer AP et al. J Pediatr Hematol Oncol 26: 761, 2004).


Gcsf leukemia mds

GCSF & leukemia/MDS

NCCN Guidelines: Myeloid Growth Factors v.1. 2009:

“Although there have been suggestions of potentially increased risk of acute leukemia with G-CSF administration from epidemiological studies, they are confounded by by differences in the chemotherapy dose delivered. The research on Adverse Drug Reports (RADAR) group concluded that long-term safety data is still lacking to confirm such a relationship (Tiggue CC et al. Bone Marrow Transplant 40: 185-192, 2007)


Csfs

Guidelines for the

use of CSFs*

* “…guidelines cannot always account for individual variations among patients. They are not intended to supplant physician judgement with respect to to particular patients or special clinical situations….”(ASCO guidelines-2006)


Asco american society for clinical oncology guidelines

ASCO(American Society for Clinical Oncology)Guidelines

2006 Update of recommendations for the use of white blood cell growth factors: an evidence-based, clinical practice guidelines. Smith TJ et al. for the American Society of Clinical Oncology Growth Factor Expert Panel.Published ahead of print on J Clin Oncol May 8, 2006


Csfs

Clinical Practice Guidelines in Oncology:

Myeloid Growth Factors

Version 1. 2009

http://www.nccn.org


Eortc european organization for research and treatment of cancer guidelines

EORTC (European Organization for Research and Treatment of Cancer) Guidelines

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia adult patients with lymphomas and solid tumors.Aapro MS et al. Published ahead of print, Europ J Cancer , 2006


Csfs

Hematopoietic growth factors: ESMO recommendations for the applications.

Greil R et al. Ann Oncol 19 (suppl 2): ii116-ii118, 2008


Csfs

Types of CSFs, Dosage & Administration


Csfs

Dosage and administration

  • Filgrastim (Neupogen) (category 1)*:

  • Daily dose of 5mcg/kg (rounding to the nearest vial size)(300 mcg/day for pts < 78 kg and 480 mcr/day for pts > 78 kg)

  • Pegfilgrastim (Neulasta = Neulastim) (category 1)*:

  • One dose of 6mg per cycle of treatment

  • (There is evidence to support use for chemotherapy regimens given every 3weeks/2 weeks)

    *Category 1: There is uniform NCCN consensus, based on high-level evidence, that the recommendation is appropriate.


Gm csf

GM-CSF

NCCN:

  • Sargramostim (GM-CSF) = (category 2B*)

    *Category 2B: …ununiform NCCN consensus (but no major disagreement)…

    ASCO:

  • ….GM-CSF has been licensed specifically for use after autologous or allogeneic BMT and for AML…


Pegfilgrastim nccn asco

Pegfilgrastim: NCCN & ASCO

NCCN (2008):

  • There is evidence to support use for chemotherapy regimens given every 3 weeks.

  • Phase II studies demonstrate efficacy in chemotherapy regimens given every 2 weeks.

  • There is insufficient data to support dose and schedule of chemptherapy schedules of less than 2 weeks, and these cannot be recommended.

    ASCO (2006):

  • The safety and efficacy has not been fully established in the setting of dose-dense chemotherapy.

  • Should not be used in children or small adolescents (< 45 kg).

  • The long-term effects of long acting growth factors are unknown---need for long-term safety data.


Lenograstim granocyte

Lenograstim (Granocyte)

Glycosylated G-CSF; produced in culture by mammalian cells; identical to the natural molecule.

Recommended dose: 1 Amp = 263 mcg/day.


Eortc guidelines for choice of formulation

EORTC guidelines for choice of formulation

“Filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated”.


Dosage administration contd

Dosage & Administration (contd)

ASCO, ESMO & NCCN:

  • Start 24-72 h after completion of chemotherapy.

  • Treat through post-nadir ANC recovery.

    The package insert suggests to continue until the occurrence of ANC-10,000 /microL after the neutrophil nadir. However, a shorter duration is sufficient (ASCO 2006: until reaching ANC of at least 2000-3000/mm3).


Non continuous less intensive g csf therapy

Non continuous (less intensive) G-CSF therapy

Papaldo P et al.J Clin Oncol23:6908-18, 2005:

  • The study was designed to evaluate the comparative efficacy of varying intensity schedules of recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) support in preventing febrile neutropenia in early breast cancer patients treated with relatively high-dose epirubicin plus cyclophosphamide (EC).

  • CONCLUSION: In the adjuvant setting, the frequency of prophylactic G-CSF administration during EC could be curtailed to only two administrations (days 8 and 12) without altering outcome. This nonrandomized trial design provides support for evaluating alternative, less intense G-CSF schedules for women with early breast cancer*.

    * Kuderer NM et al. J Clin Oncol 25:3158-67, 2007 (a systematic review):“ a nonrandomized post hoc analysis of different interrupted G-CSF strategies in pts with low risk of febrile neutropenia. Interruption of growth factor administration before adequate neutrophil recovery seems not to be effective in higher risk settings…whereas trials using uninterrupted treatment according to current guidelines have clearly demonstrated the efficacy of G-CSF in this setting”


Csfs

For peripheral blood stem cell collection (PBPC) the filgrastim dose is 10/mcg/kg/day.


Csfs

Primary & secondary prophylaxis


Asco guidelines for primary prophylaxis

ASCO guidelines for primary prophylaxis

  • When the risk of febrile neutropenia is approximately 20% or more (not>40% as in 2000 guidelines) and no other equally effective regimen that does not require GCSF is available.


Csfs

Prophylactic use of CSFs

  • “Over the last decade, the costs of inpatient

    hospitalization have escalated, changing the risk threshold on a pure cost basis from 40% to

    approximately 20%”.

  • More importantly, several randomized studies have documented clinical benefits of CSFs in lower risk populations.


Csfs

Vogel CL et al. J Clin Oncol 23: 1178-84, 2005:

Docetaxel (taxotere) 100 mg/m2 q 3wks in breast cancer

Randomized: pegfilgratim administered 24 hrs after chemotherapy vs. placebo

Overall incidence of febrile neutropenia:1% vs. 17% (p< 0.001).

Overall incidence of hospitalization: 1% vs. 14% (p< 0.001).

Pegfilgrastim is effective in preventing febrile neutropenia resulting from moderately myelosuppressive chemotherapy


Asco primary prophylaxis contd

ASCO/primary prophylaxis(contd)

  • For “dose-dense” regimens CSFs are required and recommended.


Asco primary prophylaxis special circumstances

ASCO/primary prophylaxis*: Special Circumstances

  • Age > 65,

  • Poor PS,

  • Previuos episodes of FN,

  • Pre-existing neutropenia due to disease,

  • Extensive prior therapy, including large radiation ports,

  • Cytopenias due to BM involvement,

  • Poor nutritional status,

  • Open wounds or active infections,

  • More advanced cancer & serious comorbidities.

    * Consider even with regimens with FN rates of < 20%.


Asco eortc guidelines csfs in older patients

ASCO& EORTC guidelines/ CSFs in older patients

ASCO:Prophylactic CSF for patients with diffuse aggressive NHL aged > 65 treated with curative chemo (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections.

EORTC: In assessing patient-related risk factors, particular consideration should be given to the elevated risk of FN in elderely pts (aged 65 or older).


Asco recommendations for secondary prophylaxis

ASCO recommendations for Secondary Prophylaxis

  • After a documented febrile neutropenia in an earlier cycle.

  • Even if febrile neutropenia has not occurred, the use of CSFs may be considered if prolonged neutropenia is causing excessive dose reduction or a delay in chemotherapy.


Csfs

Prophylactic use of CSFs

Re-evaluate patient every cycle for treatment intent and risk categorization.


Csfs

Prophylactic use of CSFs

The decision to use prophylactic CSFs is based on the:

  • Type of chemotherapy,

  • patient's risk factors,

  • Treatment intent:

    -curative/adjuvant

    -prolong survival

    -symptom management


Csfs

NCCN Indications for prophylactic CSF according to type of chemotherapy treatment intent and risk of febrile neutropenia (applies to the first and all subsequent cycles)


Nccn high risk 20 probability of febrile neutropenia or a neutropenic event compromising treatment

Curative/adjuvant & prolong survival and

Quality of life:

Routine use is recommended (category 1*).

*Category 1: There is uniform NCCN consensus, based on high-level evidence, that the recommendation is appropriate.

Symptom management/quality of life:

The use of high dose chemotherapy in this setting is a difficult decision and requires careful discussion between the physician and the patient…

NCCN-high risk (>20% probability of febrile neutropenia or a neutropenic event compromising treatment)


Csfs

NCCN- intermediate risk (10-20% probability of febrile neutropenia or a neutropenic event compromising treatment)

Curative/adjuvant:

Consider CSF:

Individualized consideration based on physician-patient discussion

Symptom management/quality of life:

Consider CSF:

The use of high dose chemotherapy in this setting is a difficult decision and requires careful discussion between the physician and the patient….


Nccn low risk 10 probability of febrile neutropenia

NCCN-low risk(<10% probability of febrile neutropenia)

Routine use of CSFs is not recommended unless the patient is receiving curative or adjuvant treatment and is at significant risk for serious medical consequences of febrile neutropenia, including death.


Nccn 2008 examples of chemotherapy regimens with a high risk of febrile neutropenia 20 1 of 2

NCCN (2008):Examples of chemotherapy regimens with a high risk of febrile neutropenia (>20%)(1 of 2)


Nccn 2008 examples of chemotherapy regimens with a high risk of febrile neutropenia 20 1 of 21

NCCN (2008):Examples of chemotherapy regimens with a high risk of febrile neutropenia (>20%)(1 of 2)


Nccn 2008 examples of chemotherapy regimens with a high risk of febrile neutropenia 20 2 of 2

NCCN (2008):Examples of chemotherapy regimens with a high risk of febrile neutropenia (>20%)(2 of 2)


Csfs

NCCN (2008):Examples of chemotherapy regimens with an intermediate risk of febrile neutropenia (10-20%)(1 of 2)


Csfs

NCCN (2008): Examples of chemotherapy regimens with an intermediate risk of febrile neutropenia (10-20%)(2 of 2)


Nccn 2008 patient risk factors for developing febrile neutropenia 1 of 2

NCCN (2008): Patient risk factors for developing febrile neutropenia (1 of 2)


Nccn 2008 patient risk factors for developing febrile neutropenia 2 of 2

NCCN (2008): Patient risk factors for developing febrile neutropenia(2 of 2)


Nccn 2008 risk factors that compromise ability to deliver full dose chemotherapy 1 of 2

NCCN (2008): Risk factors that compromise ability to deliver full-dose chemotherapy (1 of 2)


Nccn 2008 risk factors that compromise ability to deliver full dose chemotherapy 2 of 2

NCCN (2008): Risk factors that compromise ability to deliver full-dose chemotherapy (2 of 2)


Csfs in dose dense or dose intense chemotherapy

CSFs in dose-dense or dose-intense chemotherapy

ASCO & EORTC: Use if such strategy has therapeutic benefit.


Csfs

CSFs in established febrile neutropenia


Csfs

CSFs for chemotherapy-induced febrile neutropenia: a meta-analysis(Clark OA et al. J Clin Oncol 23: 4198-4214, 2005)

  • Significantly reduces the length of hospitalizationand the time to neutrophil recovery.

  • A marginally significant result was obtained for the use of CSF in reducing infection-related mortality.


Asco guidelines for g csf therapy febrile patients with neutropenia

ASCO Guidelines for G-CSF Therapy- Febrile Patients with neutropenia

High-risk patients in whom G-CSF may be considered:

  • Expected prolonged (> 10 d) and profound neutropenia (ANC < 100/microliter)

  • Age > 65

  • Fever of > 10 days in duration

  • Pneumia, hypotension and multiple organ failure (sepsis syndrome)

  • Multi-organ dysfunction

  • Invasive fungal infection

  • Uncontrolled malignancy

  • Being hospitalized at the time of the development of fever


Esmo guidelines for g csf therapy febrile patients with neutropenia

ESMO Guidelines for G-CSF Therapy- Febrile Patients with neutropenia

  • Protracted febrile neutropenia (> 7 days)

  • OR: hypotension or sepsis

  • OR: pneumonia or fungal infection


Eortc guidelines for g csf therapy febrile patients with neutropenia

EORTC Guidelines for G-CSF Therapy- Febrile Patients with neutropenia

“…limited to those pts who are not responding to appropriate antibiotic management and who are developing life-threatening infections (such as severe sepsis or septic shock).”


Asco csf in patients with afebrile neutropenia

ASCO/ CSF in patients with afebrile neutropenia

  • ….should not routinely be used.


Asco use of csf in patients receiving radiotherapy

ASCO/Use of CSF in patients receiving radiotherapy

  • Avoids in pts receiving concomitant chemo and radiotherapy, particularly involving the mediastinum.

  • Consider in pts receiving radiotherapy alone if prolonged delays, secondary to neutropenia, are expected.


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