Guideline for the use of granulocyte-colony stimulating factor (G-CSF) in adult oncology and haematology patients

Transcription

1 Cumbria, Nrthumberland, Tyne & Wear Area Team Guideline fr the use f granulcyte-clny stimulating factr (G-CSF) in adult nclgy and haematlgy patients Dcument Cntrl Prepared By Issue Date Apprved By Review Date Versin Cntributrs Cmments/ Amendment S Williamsn / Chemtherapy W Hrsley Grup Calum Plwart S.Williamsn Chemtherapy Grup Gail Jnes Updated sectin 3.5 S Williamsn Chemtherapy Grup Will Hrsley Inclusin f Lipegfilgrastim and assciated guidance Acknwledgements This guidance has been based upn Yrkshire Cancer Netwrk plicy, whse authr David Thmsn, kindly agreed fr the plicy t becme basis f lcal NHS England/ Netwrk Guidance, fllwing changes in cmmissining arrangements fr GCSF prducts frm 1 st April 2014 GCSF Guidelines June 2014 v1.41 Page 1 f 11 Apprved Expiry 30th June 2016

2 i Table f Cntents I TABLE OF CONTENTS INTRODUCTION INDICATIONS FOR G-CSF USE CRITERIA FOR G-CSF PRESCRIBING CRITERIA 1A: CHEMOTHERAPY SUPPORT FOR REGIMENS WITH CURATIVE/ RADICAL INTENT: PRIMARY PROPHYLAXIS (FIRST AND SUBSEQUENT CYCLE USE) CRITERIA 1B: CHEMOTHERAPY SUPPORT FOR REGIMENS WITH CURATIVE/ RADICAL INTENT: SECONDARY PROPHYLAXIS (PROPHYLACTIC USE IN SUBSEQUENT CYCLES AFTER INITIAL EPISODE(S) OF SEVERE AND/ OR FEBRILE NEUTROPENIA) CRITERIA 2: SUPPORTIVE THERAPY FOR SEVERE NEUTROPENIC SEPSIS CRITERIA 3: PERIPHERAL BLOOD STEM CELL MOBILISATION Backgrund Dsing CRITERIA 4: PERIPHERAL BLOOD STEM CELL TRANSPLANTATION Pst peripheral bld stem cell transplantatin Duratin f treatment CRITERIA 5: GRAFT FAILURE POST STEM CELL TRANSPLANTATION CRITERIA 4: CLINICAL TRIALS WHERE APPROPRIATE AND STATED WITHIN THE TRIAL PROTOCOL APPROVAL TO PRESCRIBE GCSF FOR ALL INDICATIONS EXCEPT IN PERIPHERAL BLOOD STEM CELL MOBILISATION FOR PERIPHERAL BLOOD STEM CELL MOBILISATION PRESCRIBING G-CSF REFERENCES GCSF Guidelines June 2014 v1.41 Page 2 f 11 Apprved Expiry 30th June 2016

3 1 Intrductin Chemtherapy-induced febrile neutrpenia is a serius side effect f cancer treatment and is nt nly a majr risk factr fr infectin-related mrbidity and mrtality, but is als a significant dse-limiting txicity. Patients develping severe (grade 3/4) r febrile neutrpenia (FN) during chemtherapy frequently receive dse reductins and/r delays t their chemtherapy schedule. This may impact n the success f treatment, particularly when treatment intent is either curative r t prlng survival (1). One methd f reducing the incidence f severe r FN is thrugh the prphylactic use f G-CSF. G-CSF may als be used t increase neutrphils in thse patients experiencing severe prlnged neutrpenic episdes after chemtherapy treatment r in thse patients requiring mbilisatin f peripheral bld stem cells fr harvesting. There are currently 3 branded CSFs available n the UK market. There is very little direct cmparative data t enable an bjective assessment between agents t be made. There are several bi-similar GCSF brands available, e.g. Ratigrastim, Tevagrastim and Zarzi. These are bi-similar filgrastim i.e. the prtein structure is very similar t the riginal Neupgen versin f filgrastim. The natinal bne marrw transplant service has recmmended against the use f bisimilar fr PBSC until further evidence f effectiveness in this setting is available. NHS England recmmends the use f Bisimilars as first chice GCSF in all settings where the Neupgen brand f filgrastim wuld therwise have been used. The chice f use f bisimilar in place f standard GCSF shuld be a lcal cmmissining decisin but shuld generally be the lwest price. NHS England des nt recmmend rutine use f lnger-acting pegalyted GCSFs such as pegfilgrastim (Neupgen ) and Lipegfilgrastim (Lnquex ). An exceptin is made fr a limited number f specific situatins. Where a lnger- acting GCSF is required prescribers shuld select the mst cst-effective treatment which in mst cases will be the preparatin with the lwest acquisitin cst. The aim f this guideline is t prvide evidence-based guidance t clinicians and ther health prfessinals n the ratinal prescribing and safe administratin f G-CSF and t prmte harmnisatin f prescribing practice. (Please nte: these guidelines d nt apply t acute leukaemia r paediatric patients fllw guidelines stated within the relevant trial prtcl). 2 Indicatins fr G-CSF use G-CSF may be prescribed fr the fllwing indicatins, accrding t the criteria fr G-CSF prescribing utlined in sectin 3: a. Chemtherapy supprt fr regimens with curative/radical intent (primary/secndary prphylaxis). b. Supprtive therapy fr severe neutrpenic sepsis. c. Peripheral bld stem cell mbilisatin. d. Clinical trials where apprpriate and stated within the trial prtcl. Nte: Patients receiving palliative chemtherapy shuld nt generally receive prphylactic G-CSF fr chemtherapy supprt manipulatins t minimise neutrpenic episdes and sepsis must initially include dse delay and/r dse reductin (refer t individual chemtherapy prtcls fr guidance) as there is n evidence that dse maintenance r escalatin imprves clinically imprtant utcmes. The use f G-CSF in this setting must be apprved n an individual patient basis accrding t lcal trust plicies fr named patient apprval f expenditure. GCSF Guidelines June 2014 v1.41 Page 3 f 11 Apprved 16 June 2014 Expiry 16 June 2016

4 3 Criteria fr G-CSF prescribing 3.1 Criteria 1A: Chemtherapy supprt fr regimens with curative/ radical intent: Primary prphylaxis (first and subsequent cycle use) Chemtherapy patients shuld nt rutinely be prescribed prphylactic G-CSF after their first cycle f chemtherapy except in the circumstances described belw. Primary prphylaxis may nly be cnsidered fr patients with a high verall risk (> 20%) f febrile neutrpenia as defined belw: Patients receiving myeltxic chemtherapy with curative r radical intent (including adjuvant/neadjuvant chemtherapy) and which has a dcumented incidence rate f FN f > 20% (see table 1) Regimen Tumur type Dcumented FN risk Reference DHAP NHL (relapsed) 48% (1), (2) ESHAP/ FLUDAP NHL Hdgkins disease Multiple Myelma 30% (1), (2) (all relapsed) All Dcetaxel-based regimens Breast (Ne-adjuvant) Breast (adjuvant) 22-36% (3), (4) (includes FEC-T) CODOX-M/ IVAC (+/-R) Burkitts Lymphma >50% (5) Mini-BEAM Hdgkins disease (relapsed) 54% (6) Table 1: Regimens with FN rate f >20% Primary prphylaxis may als be cnsidered in: Patients receiving myeltxic chemtherapy with curative/radical intent (including adjuvant/neadjuvant chemtherapy) and which has a dcumented incidence rate f FN f 10 20% (see table 2) AND any ne r mre f the fllwing pre-dispsing patient risk factrs (1): Patient age > 65 years Pr perfrmance status Previus episdes f febrile neutrpenia Extensive prir treatment including large radiatin prts Administratin f cmbined chemraditherapy Bne marrw invlvement by tumur-prducing cytpenias Pr nutritinal status The presence f pen wunds r active infectins Mre advanced cancer Other serius c-mrbidities GCSF Guidelines June 2014 v1.41 Page 4 f 11 Apprved 16 June 2014 Expiry 16 June 2016

5 Regimen Epi-CMF (Epi nly) BEP EP Carb/Etpside POMB-ACE TIP VIP Stanfrd V CHOP 21 FMD IVE R-CHOP 21 Tumur type Breast Hdgkins disease NHL NHL NHL (relapsed) NHL Table 2: Regimens with FN rate f 10-20% The G-CSF f chice fr primary prphylaxis in CNTW Area Team is daily G-CSF in the frm f the bisimilar Filgrastim. Occasinally the use f a lnger-acting pegylated G-CSF as primary prphylaxis may be cnsidered e.g. patients wh cannt be taught r are incapable t self-inject r fr whm there is nt a suitable carer available t inject with daily G-CSF. GCSF dsage and administratin guidelines in the prphylactic setting. Because the kinetics f myeltxicity and recvery f bne marrw functin vary between cyttxic agents and regimens, universal recmmendatins n this subject cannt be made. There is sme evidence that treatment sn after chemtherapy may be mre beneficial than later, althugh, f curse, G-CSF is cntraindicated within 24 hurs f chemtherapy, when stimulatin f prgenitr cells in the presence f cyttxics may actually wrsen the myeltxicity f the regimen. Fr cyttxic drugs with a lng half life, a lnger interval may be required t avid increased myeltxicity. A reasnable starting pint fr GCSF is t start nt less than 24 hurs and nt mre than 72 hurs after cyttxic treatment is cmpleted. This ensures that the stimulus prvided is present at a time when the bne marrw is regenerative and able t respnd. G-CSF injectins shuld cntinue until the neutrphil cunt has recvered t > 1.0 x 10 9 /L n tw cnsecutive days. This will nrmally require a minimum f 5 days f treatment, althugh cnsideratin shuld be given t a minimum f 7 days fr mre myelsuppressive regimens studies lking at NHL patients receiving myelsuppressive chemtherapy shwed that patients receiving 5 dses f G-CSF had abut 3 times the risk f febrile neutrpenia and hspitalizatin than thse wh received a 10 day curse (7,8). It is nt expected that every patient has serial FBC tests, rather that adjustments t the duratin f therapy are made based n clinical expertise and past respnse f the patient t GCSF. See table 3 belw fr GCSF dsage and administratin guidelines in the prphylactic setting. GCSF Guidelines June 2014 v1.41 Page 5 f 11 Apprved 16 June 2014 Expiry 16 June 2016

6 Drug Bisimilar Filgrastim (Zarzi ) Lipegfilgrastim (Lnquex ) r Pegfilgrastim (Neulasta ) Patient weight <78kg 78kg Dse 30MU 48MU Rute Frequency sc Once daily All 6mg sc Single dse Weekly chem cycle Days t prescribe (see nte 1) 3 2 weekly weekly chem chem cycle cycle 4 weekly chem cycle Initiate G-CSF 24-72hrs after administratin f chemtherapy unless therwise specified in the chemtherapy prtcl Cntinue until after nadir and ANC 1.0 X 10 9 /L r as per chemtherapy prtcl. Nt recmm ended One dse is recmmended fr each chemtherapy cycle, administered apprximately 24 hurs fllwing cyttxic chemtherapy Table 3: G-CSF Dsage and Administratin Guidelines fr patients fulfilling criteria 1A/1B Nte 1: The ptimal timing and duratin f G-CSF administratin in the prphylactic setting has nt been defined hwever the recmmendatins abve shuld be cnsidered as a guide. GCSF Guidelines June 2014 v1.41 Page 6 f 11 Apprved 16 June 2014 Expiry 16 June 2016

7 3.2 Criteria 1B: Chemtherapy supprt fr regimens with curative/ radical intent: Secndary prphylaxis (prphylactic use in subsequent cycles after initial episde(s) f severe and/ r febrile neutrpenia) Secndary prphylaxis shuld nly be cnsidered in patients: Receiving myeltxic chemtherapy with curative r radical intent And where further treatment delays r dse reductins may cmprmise the intended treatment utcme, fr example in any ne f the fllwing circumstances: Where tw r mre dse reductins have ccurred due t neutrpenia r febrile neutrpenia after a chemtherapy cycle Where chemtherapy treatment is delayed n tw r mre ccasins due t neutrpenia r febrile neutrpenia Nte: Dse mdificatins will be a reasnable alternative in many clinical situatins. Secndary prphylaxis may nly be cnsidered after ne delay in chemtherapy treatment r ne dse reductin due t an episde f neutrpenia r febrile neutrpenia fr the fllwing patient grups where dse reductin/ dse delay wuld cmprmise disease free r verall survival: Adjuvant breast cancer Lymphma (nn-hdgkins lymphma r hdgkins disease) malignancies Ne-adjuvant chemtherapy Limited stage small cell lung cancer Radical chemradiatin (where delay r missin f chemtherapy treatment during cncurrent therapy may have a negative impact n disease cntrl) Multiple myelma The G-CSF f chice fr secndary prphylaxis in CNTW is daily G-CSF in the frm f the bisimilar Filgrastim. Occasinally the use f a lnger-acting pegylated G-CSF as primary prphylaxis may be cnsidered e.g. patients wh cannt be taught r are incapable t self-inject r fr whm there is nt a suitable carer available t inject with daily G-CSF. Refer t table 3 fr GCSF dsage and administratin guidelines in the prphylactic setting. GCSF Guidelines June 2014 v1.41 Page 7 f 11 Apprved 16 June 2014 Expiry 16 June 2016

8 3.3 Criteria 2: Supprtive therapy fr severe neutrpenic sepsis G-CSF must nt be rutinely prescribed fr the treatment f patients with uncmplicated febrile neutrpenia r afebrile neutrpenia. G-CSF may nly be prescribed fr the supprtive treatment f patients with severe febrile neutrpenia in scenaris as defined belw: Prfund febrile neutrpenia: defined as abslute neutrphil cunt (ANC) < 0.1 x 10 9 /L and patient febrile And any ne f the fllwing prgnstic factrs that are predictive f pr clinical utcme: Clinically unwell with signs such as hyptensin, rgan dysfunctin etc indicating ptential risk f septic shck Expected prlnged duratin f neutrpenia (> 10 days) Persistent pyrexia despite apprpriate antibitics/antifungals Uncntrlled primary disease Pneumnia Prven r suspected invasive fungal infectin Patients treated with a lnger-acting pegylated G-CSF shuld nt be treated with additinal G-CSF. In additin, there is currently a lack f evidence fr therapeutic (rather than prphylactic) use f lnger-acting G-CSF (3). Refer t table 4 fr GCSF dsage and administratin guidelines in the neutrpenic sepsis setting. Table 4: G-CSF Dsage and Administratin Guidelines fr patients fulfilling criteria 2 Patient Drug Weight r BSA Dsage Rute Frequency Bisimilar Filgrastim (Zarzi) <78kg 78kg 30MU 48MU sc Once daily Criteria fr stpping treatment Stp G-CSF nce ANC > 0.5 x 10 9 /L fr at least tw cnsecutive days Nte: Lnger-acting Pegylated G-CSF is nt apprved fr use in this setting GCSF Guidelines June 2014 v1.41 Page 8 f 11 Apprved 16 June 2014 Expiry 16 June 2016

9 3.4 Criteria 3: Peripheral bld stem cell mbilisatin Backgrund Guidelines fr apprval f bisimilars have been issued by the EMEA (9) and vary accrding t the prduct. In general, the apprval f bisimilars is based n the demnstratin f equivalent efficacy and safety t the innvatr prduct in cmparative studies. In the case f G-CSF, equivalence has t be demnstrated in the prphylaxis f severe cyttxic chemtherapy-induced neutrpenia and extraplatin f efficacy t the ther indicatins f the reference prduct (e.g. mbilizatin f stem cells) is then allwed. Because there is a limited clinical database n apprval f a bisimilar ( patients app.), pharmacvigilance is becming essential, particularly as nly six-mnth fllw up is needed fr safety in registratin studies. Therefre the EBMT recmmends evaluatin f efficacy and safety data fr stem cell mbilizatin befre using bisimilar G-CSF in healthy dnrs. This can nly be btained by perfrming clinical trials with an adequate number f stem cell mbilizatin prcedures with adequate fllw up in autlgus cnditins. Until studies have been perfrmed t prvide the required efficacy and safety data, the EBMT des nt recmmend the use f bisimilar G-CSFs fr mbilizatin f stem cells in healthy dnrs fr stem cell transplantatin (10). The same advice shuld be cnsidered fr autlgus stem cell mbilisatin Dsing Fr patients nt in a study, Lengrastim (GRANOCYTE ) shuld be used at the dsing schedule in the manufacturers SPC. Lengrastim (GRANOCYTE ) shuld be prescribed t all patients underging harvesting f peripheral bld stem cells. Nte: Lnger-acting Pegylated G-CSF is nt apprved fr use in this setting. 3.5 Criteria 4: Peripheral bld stem cell transplantatin Pst peripheral bld stem cell transplantatin If indicated patients shuld receive bisimilar Filgrastim at the daily dsing schedule in the manufacturers SPC accrding t patients weight. Nte pst-autgraft patients are at >20% FN risk, use f GCSF has the ptential t save 1-2 bed days per transplant Duratin f treatment Autlgus transplants - Stp the G-CSF after 2 cnsecutive days f neutrphils >1.0 x 10 9 /l. Nte: Lnger-acting Pegylated G-CSF is nt apprved fr use in this setting. GCSF Guidelines June 2014 v1.41 Page 9 f 11 Apprved 16 June 2014 Expiry 16 June 2016

10 3.6 Criteria 5: Graft failure pst stem cell transplantatin G-CSF may be prescribed t patients receiving chemtherapy with radical r curative intent wh are being treated within a clinical trial and where G-CSF is recmmended r allcated as part f the trial prtcl. In the setting f graft failure pst stem cell transplantatin (i.e. after satisfactry engraftment, neutrpenia develps), supprt with a trial f haematpietic grwth factrs may reslve the graft failure. 3.7 Criteria 4: Clinical trials where apprpriate and stated within the trial prtcl G-CSF may be prescribed t patients receiving chemtherapy with radical r curative intent wh are being treated within a clinical trial and where G-CSF is recmmended r allcated as part f the trial prtcl. The G-CSF brand, dsage and administratin schedule used within a clinical trial shuld be that recmmended within the trial prtcl. 4 Apprval t prescribe GCSF 4.1 Fr all indicatins EXCEPT in peripheral bld stem cell mbilisatin Unless a regimen listed in sectins r specified in a chemtherapy prtcl that has been agreed by the Netwrk Chemtherapy Grup a cnsultant nclgist/haematlgist, assciate specialist r specialist registrar must authrise G-CSF treatment accrding t the abve recmmendatins but it may be prescribed by any member f the clinical team and the indicatin must be dcumented in the patient s medical ntes. 4.2 Fr peripheral bld stem cell mbilisatin Any member f the haematlgy medical team may prescribe G-CSF accrding t the apprpriate prtcl fr the particular patient. 4.3 Prescribing G-CSF In rder t ensure that the crrect prduct is administered, it is vital t specifiy the brand f GCSF required n the prescriptin. We wuld suggest prescribing by brand name nly. GCSF Guidelines June 2014 v1.41 Page 10 f 11 Apprved 16 June 2014 Expiry 16 June 2016

11 5 References (1) Aapr et al Update f EORTC guidelines fr the use f granulcyte-clny stimulating factr t reduce the incidence f chemtherapy-induced febrile neutrpenia in adult patients with lymphprliferative disrders and slid tumurs. Eur J Cancer 47 (2001): (2) Smith et al Update f Recmmendatins fr the Use f White Bld Cell Grwth Factrs: An Evidence-Based Clinical Practice Guideline. J Clin Oncl July ; 24 (19): (3) Natinal Cmprehensive Cancer Netwrk (NCCN) Clinical Practice Guidelines in Onclgy (2011). Myelid Grwth Factrs. V.I.2011 (4) MacDermtt, C. Febrile Neutrpenia in patients receiving adjuvant/ neadjuvant dcetaxel fr breast cancer Audit f Bradfrd Ryal Infirmary experience. Data n file. Octr 2011 (5) Mead, GM, et al. An internatinal evaluatin f CODOX-M and CODOX-M alternating with IVAC in adult Burkitts lymphma: results f United Kingdm Lymphma Grup LY06 study. Ann Oncl, (8): p (6) Clwill R, et al. Mini-BEAM as salvage therapy fr relapsed r refractry Hdgkin's disease befre intensive therapy and autlgus bne marrw transplantatin. J Clin Oncl February 1, 1995 vl. 13 n (7) Sctt, SD et al; J Manag Care Pharm 2003; 9: (8) Weycker, D et al; Prc ASCO 2004; 23: 613 Abstract 6731 (9) EMEA Cmmittee Fr Medicinal Prducts Fr Human Use (CHMP); Annex T Guideline On Similar Bilgical Medicinal Prducts Cntaining Bitechnlgy-Derived Prteins As Active Substance: On-Clinical And Clinical Issues - Guidance On Similar Medicinal Prducts Cntaining Recmbinant Granulcyte-Clny Stimulating Factr; 2006 (10) EBMT Stance n the Apprval f a G-CSF Bisimilar, 2009 (11) (Lnquex ) lipegfilgrastim Summary prduct Characteristics May 2013 (data n file) GCSF Guidelines June 2014 v1.41 Page 11 f 11 Apprved 16 June 2014 Expiry 16 June 2016