Electronic Supplementary Material
Efficacy, effectiveness and safety of long-acting granulocyte colonystimulating factors for prophylaxis of chemotherapy-induced neutropenia
in patients with cancer: a systematic review
Alena M. Pfeil1, Kim Allcott2, Ruth Pettengell3, Gunter von Minckwitz4, Matthias
Schwenkglenks1*, Zsolt Szabo5*
1 Institute of Pharmaceutical Medicine, University of Basel, Basel, Switzerland
2 Oxford PharmaGenesis™ Ltd, Oxford, UK
3 Cellular and Molecular Medicine, St. George’s University of London, London, UK
4 German Breast Group, Neu-Isenburg and University of Frankfurt, Frankfurt, Germany
5 Clinical Development, Amgen Europe GmbH, Zug, Switzerland
* Joint last authorship
Correspondence
Alena M. Pfeil, MSc
PhD Student / Research Associate
Institute of Pharmaceutical Medicine (ECPM)
University of Basel
Klingelbergstrasse 61
4056 Basel
Switzerland
Phone: +41 61 267 19 41
Fax: +41 61 267 19 48
Email: alena.pfeil@unibas.ch
ESM 1
Detailed search strategy
Searches EMBASE
Hits
#1 exp recombinant granulocyte colony stimulating factor/ or filgrastim.mp.
12170
#2 pegylat*.mp.
12216
#3 1 and 2
#4 ($pegfilgrastim or SD01 or neulasta or neulastim or imupeg).mp.
#5 (PEG-rmetHuG-CSF or polyethylene glycol-conjugated filgrastim).mp.
392
1150
2
#6
(balugrastim or CG-10639 or lipegfilgrastim or XM-22 or glycopegylated CCSF).mp.
5
#7
(lonquex or neugranin or albugranin or SPI-2012 or LAPS-GCSF or
HM10460A).mp.
6
#8 (Extimia or BCD-017).mp.
#9 3 or 4 or 5 or 6 or 7 or 8
#10 exp cancer chemotherapy/ or exp chemotherapy/ or chemotherapy.mp.
0
1381
491608
#11 cancer.mp. or exp neoplasm/
3447398
#12 (tumor or tumour).mp.
1939478
#13 10 or 11 or 12
3783824
#14
exp neutropenia/ or neutropenia.mp. or exp febrile neutropenia/ or exp severe
congenital neutropenia/
73934
#15 9 and 13 and 14
734
#16 limit 15 to (human and english language)
578
Searches MEDLINE & MEDLINE InProcess
Hits
#1
exp Granulocyte Colony-Stimulating Factor/
28724
#2
$filgrastim.mp.
#3
pegylat*.mp.
12216
#4
(1 or 2) and 3
442
#5
($pegfilgrastim or SD01 or neulasta or neulastim or imupeg).mp.
#6
(PEG-rmetHuG-CSF or polyethylene glycol-conjugated filgrastim).mp.
2
#7
(balugrastim or CG-10639 or lipegfilgrastim or XM-22 or glycopegylated CCSF).mp.
5
#8
(lonquex or neugranin or albugranin or SPI-2012 or LAPS-GCSF or
HM10460A).mp.
6
#9
(Extimia or BCD-017).mp.
0
#10
5 or 6 or 7 or 8 or 9
#11
chemotherapy.mp.
#12
cancer.mp. or exp Neoplasms/
#13
oncology.mp. or exp Medical Oncology/
#14
(tumor or tumour).mp.
1939478
#15
11 or 12 or 13 or 14
3795647
#16
neutropenia.mp. or exp Neutropenia/
#17
10 and 15 and 16
675
#18
limit 17 to (human and english language)
532
3198
1150
1159
459728
3447398
143668
73934
Search Cochrane Library
Hits
#1
MeSH descriptor: [Granulocyte Colony-Stimulating Factor] explode all trees
1018
#2
*filgrastim
653
#3
pegylat*
959
#4
(#1 or #2) and #3
#5
$pegfilgrastim or SD01 or neulasta or neulastim or imupeg
#6
PEG-rmetHuG-CSF or polyethylene glycol-conjugated filgrastim
#7
balugrastim or CG-10639 or lipegfilgrastim or XM-22 or glycopegylated CCSF
#8
lonquex or neugranin or albugranin or SPI-2012 or LAPS-GCSF or
HM10460A
0
#9
Extimia or BCD-017
0
#10
#4 or #5 or #6 or #7 or #8 or #9
#11
chemotherapy
31372
#12
MeSH descriptor: [Neoplasms] explode all trees
44664
#13
cancer or oncology
73625
#14
MeSH descriptor: [Medical Oncology] explode all trees
#15
tumor or tumour
20482
#16
#11 or #12 or #13 or #14 or #15
91759
#17
MeSH descriptor: [Neutropenia] explode all trees
1346
#18
neutropenia
3855
#19
#17 or #18
3855
#20
#10 and #16 and #19
34
136
1
144
302
175
82
ESM 2
Definitions of outcome measures
Outcome
Definition
Febrile
neutropenia
- oral temperature ≥ 38°C and ANC <0.5x10 /L
- oral temperature ≥ 38°C for more than 1h and ANC
<0.5x109/L
- oral temperature ≥ 38.2°C and ANC <0.5x109/L
- oral temperature ≥ 38.3°C and ANC <0.5x10 9/L
- oral temperature ≥ 38.5°C and ANC <0.5x10 9/L
- oral temperature ≥ 38°C and ANC <1.0x10 9/L
- oral temperature ≥ 38.2°C and ANC <1.0x10 9/L
- oral temperature ≥ 38.3°C and ANC <1.0x10 9/L
- oral temperature > 38.5°C and ANC <1.0x10 9/L
[3,5,22,57]
[9,25,26,39,41]
Neutropenia
- Grade 3/4 or severe: ANC <1.0x109/L
- Grade 4 or severe: ANC <0.5x109/L
[3,5,6,24,39,44,50,51,57]
[5,6,21,30,39,44,60]
Hospitalisation
- due to infection ICD-9-CM 001.x-139.x
- due to febrile neutropenia ICD-9-CM 288.0 and ICD-9-CM
780.6
- neutropenia ICD-9-CM 288.0 or fever ICD-9-CM 780.6
[23]
[23]
- dose reductions (≥15% of standard doses)
- (1-dose received/dose planned)%
- dose reduction (<80% of chemotherapy dose in cycle 1)
- dose delays (≥7 days)
- dose delays (>3 days)
- full dose on schedule (≤15% dose reduction and ≤3 days dose
delay)
- planned dose on time (≥80% of planned dose and ≤3 days dose
delay)
[3,4,10,42]
[41]
[5]
[5,42]
[3,4,10,41]
[51]
Chemotherapy
dose delivery
Adverse events
Used by
9
[21,30,42,44,59]
[9,10,39,41]
[25,31,57]
[5,16,62]
[24,44]
[39]
[62]
[26,40]
[59]
CTCAE v.3.0
[6,36,38,47]
CTCAE V.4
[42]
WHO toxicity criteria
[59]
ANC, absolute neutrophil count; CTCAE, Common Terminology Criteria for Adverse Events; ICD,
International Classification of Diseases, Ninth Revision, Clinical Modification; WHO, World health
organization
ESM 3
Studies selected for full text evaluation
Author
(Year)
Journal
(Reference)
Haematological malignancies
Derbel, O.
Hematology
(2010)
(15(3):125-31)
Tumour Type
(Stage)
AML
Chemotherapy
regimens
etoposide,
methotrexate, and
actinomycin D
(EMA)
Kunivayalil
(2009)
JCO ASCO
(27,(suppl;
abstr e18005))
AML
Braess, J.
(2009)
Blood
(113(17):3903
-10)
AML (de novo)
AraC and
mitoxantrone
Sierra, J.
(2008)
BMC Cancer
(8(195))
AML (lowintermediate)
idarubicin +
cytarabine
Arthur, C. K.
(2011)
Blood ASH
(118(21))
cytarabine and
thioguanine
Faderl, S.
(2010)
Leukemia
Research (34
(3):284-288)
AML
(relapsed/refr
actory or de
novo)
CLL
fludarabine,
cyclophosphamide,
mitoxantrone
(FCM-R)
Study objectives (primary)
Patient
numbers
G-CSF Interventions
Study design
efficacy of single dose pegfilgrastim
for supporting neutrophil recovery in
acute myeloid leukaemia treated by
the EMA 2000 schedule
to compare single-dose pegfilgrastim
with filgrastim
pegfilgrastim
56 entered
study
open-label
pegfilgrastim 6 mg
filgrastim 5 μg/kg
unclear
Determine treatment efficacy and
duration of neutropenia of AraC and
mitoxantrone dose density with
pegfilgrastim in de novo AML
A single dose of pegfilgrastim
compared with daily filgrastim for
supporting neutrophil recovery in
patients treated for low-tointermediate risk acute myeloid
leukaemia
efficacy of prolonged cytotoxic
exposure in elderly AML patients
pegfilgrastim
(8 patients
treated in
pegfilgrastim
group)
172
pegfilgrastim
filgrastim
84
pegfilgrastim
(n = 42)
filgrastim (n =
41)
randomised,
double-blind,
phase 2
pegfilgrastim
filgrastim
14 (total)
retrospective
, singlecentre
efficacy of chemoimmunotherapy
over chemotherapy in treating CLL
pegfilgrastim
30
RCT
open-label
Stilgenbauer
(2011)
Blood ASH
(118: Abstract
2854)
CLL
alemtuzumab +
dexamethasone
Zagoskina
(2012)
Haematologic
a (EHA)
CLL
fludarabine and
alemtuzumab
Bouvet, E.
(2011)
Blood ASH
(118(21))
CLL (Binet
stage)
Blum, K. A.
(2011)
Blood ASH
(118(21))
Vieira, S.
(2012)
Bone Marrow
Transplantatio
n (Conference:
38th EBMT:
47:S473-S474)
Younes, A.
(2006)
European
Journal of
Cancer (42
(17):29762981)
CLL (relapsed
73% patients
rai stage 3-4)
Haematologic
al
malignancies,
acute
leukaemia,
NHL
HL
fludarabinecyclophosphamiderituximab (FCR)
frontline
flavopiridol
Cocorocchio
, E. (2010)
ecancermedic
alscience (4
(1)(184))
HL (64
patients (78%)
low risk
15 (18%)
intermediate
risk
to achieve a higher overall response
rate by adding high-dose
dexamethasone to alemtuzumab
and, simultaneously, investigating
the consolidation effect of prolonged
alemtuzumab maintenance or
allogeneic stem-cell transplantation,
respectively
to study the efficiency and toxicity of
the combination of fludarabine and
alemtuzumab (FluCam)
pegfilgrastim (6mg) D1
and D15
124
(recruited)
120 (eligible)
All patients
treated with
pegfilgrastim
prospective,
phase 2
pegfilgrastim (6mg) D6
Unclear
G-CSF impact on survivals, outcomes,
overall response rates, and toxicities
in CLL patients undergoing FCR
pegfilgrastim
no treatment
24 (included)
All patients
treated with
pegfilgrastim
101 (total)
Phase 1 trial of flavopiridol and
lenalidomide combination therapy in
relapsed CLL
explore whether Neulasta could be
useful in other chemotherapy
treatments
pegfilgrastim 24hr after
chemotherapy (D18 of
cycles 2-8)
pegfilgrastim
30 enrolled
34
prospective,
open-label,
phase 1
retrospective
doxorubicin,
bleomycin,
vinblastine, and
decarbazine (ABVD)
safety and efficacy of once-per-cycle
pegfilgrastim in support of ABVD
chemotherapy in patients with
Hodgkin lymphoma
pegfilgrastim (6mg) 24hr
after chemotherapy
23
prospective
chlorambucil,
vinblastine,
procarbazine
(ChlVPP/ABVVP)
feasibility, toxicity and efficacy of an
intensified six-cycle ChlVPP/ABVVP
regimen in advanced Hodgkin
lymphoma (HL)
pegfilgrastim
82
open-label
R-CHOP
retrospective
3 (4%) high
risk)
Engert, A.
(2006),
(2005)
Lane, S. W.
(2006)
Haematologic
a, Journal of
Supportive
Oncology (91
(4):546-549, 3
(2 SUPPL.
1):48-49)
Leukemia and
Lymphoma
(47 (9):18131817)
Noga, S. J.
(2007)
HL (high risk)
lymphoma
bleomycin,
etoposide,
doxorubicin,
cyclophosphamide,
vincristine,
procarbazine
(BEACOPP)
cyclophosphamide,
vincristine,
doxorubicin (hyperCVAD), cytarabine
lymphoma
Tilly (2011)
Blood ASH
(118: Abstract
1632)
lymphoma
R-CHOP +
lenalidomide
Woods
(2010)
JCO ASCO (28,
2010 (suppl;
abstr e18562))
lymphoma
CHOP
feasibility of pegfilgrastim support to
enable full dose of BEACOPP
chemotherapy every 14 days on
schedule
pegfilgrastim day 4
pegfilgrastim day 8
41 enrolled,
27 assessed
randomised,
(response
assessed
retrospective
ly) phase 2
safety and efficacy of pegfilgrastim
compared to granulocyte colony
stimulating factor (G-CSF) supporting
a dose-intensive, rapidly cycling antimetabolite containing chemotherapy
regimen (Hyper-CVAD) for lymphoid
malignancy
Estimate the incidence of
neutropenic complications in
patients receiving pegfilgrastim from
the first myelosuppressive
chemotherapy cycle in a communitybased setting.
pegfilgrastim (6mg)
filgrastim (5μg/kg/d)
43
pegfilgrastim
38 daily G-CSF
retrospective
analysis
pegfilgrastim (6mg) 24hr
after chemotherapy
Linked to
Noga 2007?
multi-centre,
open label,
single arm
to determine the recommended
dose of lenalinomide when given in
combination with R-CHOP-21 for
patients with previously untreated
CD20+ B-cell lymphoma
to determine whether same day
pegfilgrastim does or does not lead
to an increase in febrile neutropenia
pegfilgrastim D4
2,249
patients, 325
patients with
non-Hodgkin
lymphoma
(NHL) and 46
patients with
Hodgkin
disease
27 (enrolled)
All patients
treated with
pegfilgrastim
193 (analyzed)
162
pegfilgrastim
day 1
31
pegfilgrastim
Retrospectiv
e
pegfilgrastim (6mg) D1
pegfilgrastim (6mg) D2
phase 1 dose
escalation
study
day 2
Salar (2010)
Haematologic
a
lymphoma (24 (61.7%))
CT
Gimeno
(2009)
Blood ASH
(114: Abstract
4752)
lymphoma (34 (58%))
CHOP ± Rituximab
Moss, J. J.
(2011)
Blood ASH
(118(21))
lymphoma
(expresses
CD20
recurrent or
refractory)
azacitidine,
cyclophosphamide,
vincristine
lymphoma
(relapsed or
refractory)
etoposide,
cisplatin, and
cytarabine
multiple
myeloma
(relapsed or
refractory)
Amrubicin
Vose, J. M.
(2003)
Dinner, S. N.
(2012)
Blood ASH
(120(21))
to evaluate the incidence of grade 34 neutropenia and febrile
neutropenia (FN) over the first four
cycles of CT regimens with high or
intermediate FN risk, and to describe
the use of G-CSF prophylaxis in
clinical practice
to evaluate retrospectively the
efficacy and safety of a modifiedCHOP (with reduced dose nonpegylated liposomal doxorubicin
(NPLD) ± R in elderly pts
evaluating the maximal tolerated
dose of azacitidine given in a
schedule intended to sensitize
lymphoma to a regimen of oral
cyclophosphamide, intravenous
vincristine, and rituximab for
patients with recurrent or refractory
lymphoma
assess the duration of grade 4
neutropenia (neutrophil count < 0.5
x 10(9)/L) after one cycle of
chemotherapy with etoposide,
methylprednisolone, cisplatin, and
cytarabine
establish the maximum tolerated
dose and toxicity profile for the
combination of amrubicin with
lenalidomide and dexamethsone.
Secondary objectives were to
determine the overall response rate,
progression free survival, and time to
tumour progression
pegfilgrastim
filgrastim
294 (analyzed)
Approx 100 on
pegfilgrastim
Prospective
observationa
l cohort
pegfilgrastim D2
30 (analyzed)
All patients
treated with
pegfilgrastim
Retrospectiv
e
pegfilgrastim (6mg) 1-2D
after chemotherapy
(D10)
13 enrolled, 8
finished
treatment, 2
unevaluable
open-label,
phase 1
pegfilgrastim (100μg/kg)
filgrastim (5μg/kg/d)
66, 33 in each
group
randomised,
multicentre,
open-label
study, phase
2
pegfilgrastim (6mg) D2
10 enrolled
open-label,
phase 1
Knop, S.
(2009)
Balducci
(2012)
Chan, A.
(2011)
George, S.
(2003)
Blood ASH
(113
(18):41374143)
Blood ASH
(120: Abstract
4880)
myeloma
(relapsed or
refractory)
doxorubicin
NHL
CHOP/CHOP-R
Asia-Pacific
Journal of
Clinical
Oncology
(7(1):75-81)
Leukemia and
Lymphoma
(44 (10):16911696)
NHL
Grigg, A.
(2003)
Ibrahim, Z.
(2011)
Lee, S.
(2013)
Lokich, J. J.
(2006)
Asia-Pacific
Journal of
Clinical
Oncology
(38th, COSA)
7:135-136.)
Supportive
Care in Cancer
(21 (3):841846)
efficacy of lenalidomide, adriamycin,
dexamethasone (RAD) regimen in
treating relapsed/refractory
myeloma
to examine the association of age
with RDI for CHOP/CHOP-R in NHL
pts receiving pegfilgrastim
pegfilgrastim
69 enrolled
open-label,
phase 1/2
pegfilgrastim
Retrospectiv
e
compare the efficacy of filgrastim
and pegfilgrastim in Asian lymphoma
patients
pegfilgrastim
filgrastim
137 (analyzed)
All patients
treated with
pegfilgrastim
204
81: filgrastim
123:
pegfilgrastim
singlecentre,
retrospective
cohort study
NHL
CHOP
Determine safety of pegfilgrastim in
NHL patients
pegfilgrastim (6mg) 24hr
after chemotherapy
29
open-label
NHL
CHOP
efficacy of pegfilgrastim Vs. filgrastim
in reducing neutropenia events in
NHL
50 (total)
open-label,
randomised,
phase 2
NHL
CHOP-like'
cyclophosphamide,
doxorubicin,
vincristine (CHOP)
24
retrospective
analysis
NHL
cyclophosphamide,
vincristine,
doxorubicin (CHOP)
assess the effect of administration
timing of the pegfilgrastim on the
development of neutropenic
episodes in relation to CHOP-like
regimen administration timing in
patients with NHL
cost-benefit and quality of life
analysis of administering G-CSF with
CHOP regimen for NHL patients
pegfilgrastim (60μg/kg
and 100μg/kg)
filgrastim (5μg/kg/d)
no treatment
pegfilgrastim D1
pegfilgrastim D2
65 (total)
retrospective
, cohort
NHL
cyclophosphamide,
vincristine,
doxorubicin
pegfilgrastim (300ug,
average of 7 doses)
filgrastim (6mg)
no treatment
pegfilgrastim D1
no treatment
10
open-label,
prospective
determine if "same day"
pegfilgrastim with CHOP
chemotherapy for non-Hodgkin
lymphoma impacts on nadir white
blood count (WBC) levels or on the
nadir day
Magro
Mazo (2010)
Haematologic
a (EHA)
NHL
CHOP-R14 and
EDOCH-R14
Ng, J. H.
(2011)
Acta
Haematologic
a (125 (3):107114)
NHL
CHOP
Page, J. H.
(2012)
Blood ASH
(120(21))
NHL
R-CHOP
Wolf, M.
(2006)
Leukemia and
Lymphoma
(47 (11):23442350)
NHL
R-CHOP
Cotto, M.
(2010)
Blood ASH
(116(21))
NHL (1-4
3-4 (54%))
R-CHOP-14
Capochiani
(2009)
Haematologic
a (EHA)
NHL (1-4)
R-CHOP-14
Cabanillas,
F. (2012)
Leukemia and
Lymphoma
(53 (10):1929-
NHL (3 (46%)
and 2-4 (56%))
R-CHOP-14
to evaluate the capacity to prevent
fever associated to neutropenia and
the recovery of highly
myelosuppressor postchemotherapy neutropenia
(1) identify clinical characteristics of
patients who develop breakthrough
FN, and (2) provide descriptive data
on the incidence of breakthrough FN
among lymphoma patients
Establish current patterns of G-CSF
use and FN occurrence among the
elderly Medicare population
receiving myelosuppressive
chemotherapy for NHL
whether pegfilgrastim support
would enable on-schedule delivery of
dose-dense cyclophosphamide,
doxorubicin, vincristine and
prednisone (CHOP-14) to elderly
patients with non-Hodgkin's
lymphoma (NHL)
efficacy of pegfilgrastim and leukine
as hematopoietic support for RCHOP chemotherapy in aggressive
NHL (phase 1 and II study)
to evaluate the feasibility of the
combination of CHOP plus Rituximab
repeated every 2 weeks (CHOP-R 14)
supported with a single
administration pegfilgrastim
efficacy of pegfilgrastim and leukine
as hematopoietic support for RCHOP chemotherapy in aggressive
pegfilgrastim (6 mg) D4
filgrastim (5ug/kg/d) for
5D
56 cycles
(analyzed)
Comparative
study
pegfilgrastim
132
singlecentre,
retrospective
cohort study
pegfilgrastim
filgrastim
all administered either
as primary, secondary or
reactive prophylaxis
pegfilgrastim
retrospective
30
open-label ,
observationa
l
pegfilgrastim (4mg) D3
and leukine (GM-CSF)
(250ug) D6, 8, 10, 13
59 enrolled,
54 evaluable
open-label,
phase 1/2
pegfilgrastim (6mg) D2
21 (enrolled)
All patients
received
pegfilgrastim
Unclear
pegfilgrastim and leukine
(GM-CSF)
59
open-label
1933)
NHL
Farhan
(2009)
Blood ASH
(114: Abstract
4773)
NHL (3-4
(64%))
R-CHOP
to assess the feasibility of delivering
R-CHOP on time every two weeks
with pegylated filgastrim (Neulasta)
support for the treatment of CD20+
aggressive NHL
determine the recommended dose
of lenalinomide when given in
combination with R-CHOP-21 for
patients with previously untreated
CD20+ B-cell lymphoma
pegfilgrastim
14 (analyzed)
All patients
treated with
pegfilgrastim
phase 2
prospective
Tilly, H.
(2011)
Blood ASH
(118(21))
NHL (B-cell
CD20+)
R-CHOP
pegfilgrastim D4
open-label,
phase 1
R2CHOP
to define the maximum tolerated
dose and efficacy of Len
administered on days 1-10 with
standard R-CHOP chemotherapy
(R2CHOP)
pegfilgrastim (6mg) D2
cyclophosphamide,
doxorubicin,
vincristine
(CHOP/CHOP-R);
cyclophosphamide,
mitoxantrone,
vincristine (CNOP)
R-CHOP
evaluate changes in oncology
practice by reviewing recent
treatment patterns for patients with
aggressive B-cell NHL at 36
community-based oncology practices
and hospitals
pegfilgrastim
filgrastim
27 enrolled
18 follicular
lymphoma
4 diffuse large
B-cell
lymphoma
3 mantle cell
lymphoma
2 indolent Bcell lymphoma
12 (enrolled,
phase 1)
25 (enrolled,
phase 1I)
All patients
treated with
pegfilgrastim
500
P: 78.6%
P&F: 9.2%
Nowakowsk
i (2011)
JCO ASCO (29:
2011 (suppl;
abstr 8015))
NHL (B-cell)
Lyman, G.
H. (2011)
Blood ASH
(118(21))
NHL (B-cell)
(aggressive)
Gonzalez
Barca
(2009)
Haematologic
a (EHA)
NHL (DLBCL)
to evaluate the efficacy and
treatment compliance of dose-dense
R-CHOP supported by pegfilgrastim
in patients with DLBCL and IPI 0-2.
pegfilgrastim (6mg) D2
68 (analyzed)
Prospective
phase 1/2
prospective
multi-centre,
retrospective
,
observationa
l
Mey, U. J.
(2007)
Noga (2009)
Herrero, J.
(2012)
Blood ASH
(114: Abstract
2692)
JCO ASCO
(30(15 SUPPL.
1))
NHL (DLBCL)
R-CHOP-14
evaluate the use of pegfilgrastim in
combination with the R-CHOP-14
regimen in a homogenous group of
previously untreated elderly patients
with DLBCL and to assess the
pharmacokinetics of pegfilgrastim
within this patient population
Not stated
pegfilgrastim (6mg) 24hr
after chemotherapy
10
open-label
NHL (DLBCL)
PLD CHOP-R
pegfilgrastim (6mg) D2
unclear
phase 2 dose
escalation
NHL (DLBCL)
(newly
diagnosed,
aggressive
1-2 (22
patients, 37%)
3 (17 patients,
29%)
4 (19 patients,
32%)
NHL (DLBCL)
(relapse)
cyclophosphamide,
vincristine, nonpegylated
liposomal
doxorubicin (RCOMP-14)
evaluate the efficacy and toxicity of
dose-dense biweekly schedule of (RCOMP-14) in patients newly
diagnosed of aggressive diffuse B cell
lymphomas (DLBCL)
pegfilgrastim D2
60 enrolled,
59 evaluable
single-arm,
open-label,
multicentre
trial, phase 2
ifosfamide,
vinorelbine,
mitoxantrone
evaluate the efficacy and tolerability
of the combination of rituximab and
NIMP in the treatment of DLBCL in
first relapse
to define the maximum tolerated
dose of lenalidomide administered
on days 1-10 with R-CHOP
chemotherapy
safety of Lenalidomide combined
with R-CHOP in initial chemotherapy
for aggressive B-cell lymphomas:
Phase 1 study
pegfilgrastim (6mg) 2D
after chemotherapy (D7)
50 enrolled,
45 reviewed
multicentre,
single-arm,
phase 2
pegfilgrastim 6mg D2
12 (enrolled)
All patients
treated with
pegfilgrastim
24 enrolled
phase 2 dose
escalation
Gyan, E.
(2010)
Blood ASH
(116(21))
Nowakowsk
i, G. S.
(2009)
Blood ASH
(114: Abstract
1669)
NHL (DLBCL,
FL) (3)
R2-CHOP
Nowakowsk
i, G. S.
(2011)
Leukemia (25
(12):18771881)
NHL (DLBCL,
FL) (newly
diagnosed,
CD20
expressing
(DLBCL)
3 (FL))
R-CHOP
pegfilgrastim D2
Linked to
Nowakowski,
2011a
open-label,
phase 1
Nowakowsk
i, G. S.
(2011a)
JCO ASCO
(29(15 SUPPL.
1))
Blum, K. A.
(2012)
Gladstone,
D. E. (2011)
Leukemia and
Lymphoma
(52 (11):20762081)
Gerecitano,
J. (2009)
Blood ASH
(114: Abstract
3708)
Gerecitano,
J. (2011)
Clinical Cancer
Research (17
(8):24932501)
NHL (DLBCL,
FL) (newly
diagnosed,
CD20
expressing
(DLBCL)
3 (FL))
NHL (DLBCL,
FL, MCL, MZL)
(3- 4 (82%))
R-CHOP
define the maximum tolerated dose
and efficacy of Lenalidomide
administered on days 1-10 with
standard R-CHOP chemotherapy:
phase 1/II
pegfilgrastim (6mg) D2
9 phase 1
32 phase 2
30 evaluable
Linked to
Nowakowski,
2011b
open-label,
phase 1/2
Ibrutinib and Rbendamustine
pegfilgrastim
11 enrolled
prospective,
open-label,
phase 1
NHL (low
grade B-cell
(42 patients),
MCL (39
patients)) (1, 2
follicular
(69%),
transformed
lymphoma
(17%), other
(15%))
NHL (MCL)
cyclophosphamide
phase 1 study to determine the
MTD, DLT, toxicities, and preliminary
efficacy of R-bendamustine in
combination with ibrutinib in
patients with relapsed/refractory
NHL
feasibility of high-dose
cyclophosphamide and rituximab for
low grade B-cell, transformed and
mantle cell lymphomas
pegfilgrastim D20
81
open-label
pegfilgrastim D2
filgrastim
55 total
10
pegfilgrastim
phase 1
dose
escalation
NHL (MCL)
(relapsed/refr
actory)
cyclophosphamide,
vincristine
to determine the safety and efficacy
of substituting bortezomib for
vincristine in standard ‘R-CVP’. A
separate safety analysis evaluated
the safety of pegfilgrastim
overlapping with Bor administration,
safety and efficacy of substituting
weekly or twice-weekly bortezomib
for vincristine in the R-CVP
(rituximab, cyclophosphamide,
vincristine, and prednisone) regimen
in patients with relapsed/refractory
pegfilgrastim D2
57 enrolled,
55 completed
Randomised
dose-finding
trial, phase 1
R-CBorP
indolent and mantle cell lymphoma
(MCL)
Brusamolino
, E. (2006)
Haematologic
a (91 (4):496502)
DLBCL (4
(52%),
untreated)
cyclophosphamide,
doxorubicin,
vincristine (RCHOP-14)
Pro, B.
(2006)
Leukemia and
Lymphoma
(47 (3):481485)
NHL
(recurrent or
refractory,
relapsed
aggressive)
paclitaxel and
topotecan
JCO ASCO (29:
2011 (suppl;
abstr 3040)),
JCO ASCO
(29(15 SUPPL.
1))
adrenocortical
, esophageal,
ES-SCLC,
gallbladder,
high-grade
neuroendocri
ne, NSCLC,
prostate
(extensive
stage)
bladder
(metastatic)
Solid
tumour
malignancie
s
Traynor, A.
M. (2011)
Brighenti,
M. (2011)
ECCO (7138)
Plimack, E.
R. (2012)
JCO ASCO
(30(15 SUPPL.
1))
bladder
(muscle
invasive)
evaluate the feasibility and toxicity of
CHOP-14, with rituximab (R-CHOP14), supported by pegfilgrastim, in
untreated diffuse large B-cell
lymphoma (DLBCL)
efficacy of a single dose of
pegfilgrastim in supporting severely
myelosuppressive regimens in
previously treated cancer patients
pegfilgrastim (6mg) D3
50 enrolled,
40 completed
open-label,
phase 2
pegfilgrastim (6mg) D6
20
open-label
AT-101 in
combination with
cisplatin and
etoposide
determine the dose limiting
toxicities, maximum tolerated dose,
pharmacokinetic profile and
preliminary anti-tumour activity of
AT-101 and cisplatin and etoposide
pegfilgrastim (6mg) D4
12 (enrolled)
All patients
treated with
pegfilgrastim
(DL1a, 2a and
3a dose levels)
phase 1 dose
escalation
study, open
label
cisplatin,
gemcitabine,
paclitaxel (CGP),
MVAC
methotrexate,
vinblastine,
doxorubicin and
cisplatin (MVAC)
to evaluate two sequential non
cross-resistant dose-dense
chemotherapy regimens
pegfilgrastim (6mg) D3
21 (included)
19 (analyzed)
phase 2
prospective,
open label
Results of Neoadjuvant accelerated
MVAC (AMVAC) in patients with
muscle invasive bladder cancer:
phase 2 study
pegfilgrastim (6mg) D2/3
44 enrolled,
33 evaluable,
30 received all
cycles at full
dose
multicentre,
phase 2
Amoroso
(2009)
Brugger, W.
(2009)
Buchner, A.
(2011)
Casas, A.
(2009)
Delbaldo
(2009)
JCO ASCO
(27:15s, 2009
(suppl; abstr
1132))
Critical
Reviews in
Oncology/He
matology (72
(3):265-269)
JCO ASCO
(29(15 SUPPL.
1))
breast
trastuzumab,
docetaxel and
oxaliplatin
to investigate the feasibility and the
safety of the 3-drug combination
given as first line chemotherapy (CT)
in HER-2-positive MBC
evaluating the application of
pegfilgrastim (proactive vs reactive)
for decreasing duration of
neutropenia in breast patients
pegfilgrastim (6mg) D3
breast
FEC100
breast
AT
efficacy and safety of fixed doses of
lipegfilgrastim compared to 6 mg of
PEGF in breast patients
pegfilgrastim (6mg)
lipegfilgrastim (3mg,
4.5mg, 6mg) all 24hr
after chemotherapy
Clinical and
Translational
Oncology (11
(12):842-848)
JCO ASCO
(27:15s, 2009
(suppl; abstr
605))
breast
CMF
efficacy of pegfilgrastim in support of
a CMF regimen in treating breast
pegfilgrastim (6mg) 24hr
after chemotherapy (D9)
breast
TEC, EC→T or T→
EC
to report the safey of patients
receiving pegfilgrastim support in a
clinical trial
pegfilgrastim (6mg) D1
pegfilgrastim at cycle 1
(proactive)
pegfilgrastim after cycle
1 (reactive)
13 (enrolled)
All patients
treated with
pegfilgrastim
59
phase 2
prospective
229 patients
screened
208
randomized:
lipegfilgrastim
3mg: 53
patients
lipegfilgrastim
4.5mg: 51
patients
lipegfilgrastim
6mg:50
patients
PEGF: 54
patients
6 patients did
not complete
study
58 enrolled,
49 completed
study
randomised,
double-blind,
active
control,
multicentre
99 (received
treatment)
79
pegfilgrastim
(safety data
phase 2
prospective
RCT
open-label,
phase 2
Gladkov, O.
(2011)
JCO ASCO
(29(15 SUPPL.
1))
breast
AT
evaluate the safety and effectiveness
of CG-10639 versus PEGF in breast
patients
Gladkov, O.
(2012)
Support Care
Cancer MASCC
(20 (Suppl
1):S1–S283)
JCO ASCO (31,
(suppl; abstr
e17572))
breast
myelosuppressive
chemotherapy
breast
doxorubicin and
docetaxel (AT)
to evaluate the safety and efficacy of
balugrastim versus pegfilgrastim in
patients receiving myelosuppressive
therapy
to compare the efficacy and safety of
balugrastim vs pegfilgrastim
Support Care
Cancer MASCC
(DOI
10.1007/s005
20-013-17983)
Support Care
Cancer MASCC
(DOI
10.1007/s005
20-013-17983)
JCO ASCO (31,
(suppl; abstr
1076))
breast
AT
breast
AT
breast
TC
American
Journal of
breast
Gladkov, O.
(2013)
Gladkov, O.
(2013)
Gladkov, O.
(2013)
Hamilton
(2013)
Hendler, D.
(2011)
to present the results of a combined
analysis of two randomized phase 3
studies comparing the efficacy and
safety of balugrastim versus
pegfilgrastim in patients receiving
myelosuppressive chemotherapy
to report the safety and tolerability
findings from an integrated analysis
of two phase 2/3 studies of
lipegfilgrastim
versus pegfilgrastim in
chemotherapy-naïve patients
to report the rate of febrile
neutropenia in patients receiving
chemotherapy with and without
pegfilgrastim
efficacy of pegfilgrastim Vs filgrastim
in breast
pegfilgrastim (6mg)
CG-10639 (formally
neugranin) (30mg, 40mg,
50mg) all 24hr after
chemotherapy
balugrastim (40 or
50mg)
pegfilgrastim (6mg) all
24hr after chemotherapy
balugrastim (40mg)
pegfilgrastim (6mg)
only reported
for these
patients)
334 (total)
78 (pilot), 256
(trial)
randomised,
multi-centre,
active
controlled,
phase 2/3
RCT
469
(randomized)
236
balugrastim
234
pegfilgrastim
470 (analyzed)
236
balugrastim
234
pegfilgrastim
RCT (pooled)
phase 3
lipegfilgrastim (6mg)
pegfilgrastim (6mg)
306 (analyzed)
151
lipegfilgrastim
155
pegfilgrastim
RCT (pooled)
phase 2/3
pegfilgrastim
no treatment
240 (analyzed)
153 on
pegfilgrastim
retrospective
review
pegfilgrastim (6mg) D2
filgrastim (300μg) D3-10
231 enrolled
prospective,
no
balugrastim
pegfilgrastim 24hr after
chemotherapy
RCT (pooled)
phase 3
Holmes, F.
A. (2002)
Jenkins, P.
(2012)
Klocker, J.
(2010)
Kumar
(2009)
Clinical
Oncology:
Cancer Clinical
Trials (34
(6):619-624)
Annals of
Oncology (13
(6):903-909)
Annals of
Oncology (23
(7) (pp 17661771)(mdr493
.)
Memo Magazine of
European
Medical
Oncology (3
(3):123-128)
JCO ASCO (27,
(suppl; abstr
e20664))
Livi, L.
(2011)
Mattioli, R.
(2009)
Clinical &
Translational
Oncology:
andomised
breast
AT
efficacy and safety profiles of onceper-cycle pegfilgrastim and daily
injection filgrastim in chemotherapyinduced neutropenia
breast
docetaxel,
adriamycin and
cyclophosphamide
(TAC)
validation of a predictive model that
identifies patients at risk of febrile
neutropenia following chemotherapy
for breast
breast
FEC100, TAC
breast
TAC
breast
doxorubicin and
cyclophosphamide
(AC),docetaxel
breast
CMF
efficacy of an individualised
algorithm for the administration of
G-CSF and anti-infectives on
neutropenic complications and
entailed dose modifications in breast
patients receiving FEC-100 or TAC
to compare the incidence of febrile
neutropenia in patients who
received pegfilgrastim on the same
day as chemotherapy versus those
who received it 24-72 hours after
chemotherapy
feasibility and incidence of
Haematological toxicity in a series of
39 breast patients treated with
doxorubicin plus cyclophosphamide
(AC) followed by docetaxel, using
prophylactic G-CSF (pegfilgrastim)
determine the feasibility of growth
factor support with once-per-cycle
pegfilgrastim in breast patients
pegfilgrastim ( 30, 60 or
100 μg/kg)
filgrastim (5μg/kg/day)
all 24hr after
chemotherapy
pegfilgrastim
multi-centre
263
retrospective
pegfilgrastim
filgrastim
lenograstim
62 (FEC-100)
56 (TAC)
retrospective
pegfilgrastim (D1)
pegfilgrastim (D2
56 (analyzed)
13 received
pegfilgrastim
on day 2
Retrospectiv
e
pegfilgrastim
39
singlecentre, open
label
pegfilgrastim (6mg)
24hr after
chemotherapy (D9)
58 enrolled,
49 completed
study
open-label,
phase 2
(11(12):8428.)
Montella, L.
(2010)
European
Journal of
Cancer Care
(19 (2):200204.)
breast
docetaxel,
epidoxorubicin,
cyclophosphamide
Mueller, U.
(2011)
European
Journal of
Cancer
(47:S149.)
breast
AT
Rader, M.
(2010)
breast
Salafet
(2013)
JCO ASCO (31,
(suppl; abstr
e20593))
breast
AT
Satheesh
(2009)
JCO ASCO (27,
(suppl; abstr
e20587))
breast
TAC
Schippinger,
W. (2006)
Oncology (70
(4):290-293)
breast
epirubicin and
docetaxel/paclitaxe
l
assess the efficacy and safety profile
of once-per-cycle pegfilgrastim in
reducing FN in breast patients
treated with docetaxel,
epidoxorubicin , cyclophosphamide
administered every 3 weeks
study pharmacokinetic and
pharmacodynamic parameters as
well as observe the safety of
balugrastim
determine whether communitybased cancer patients treated with
myelosuppressive chemotherapy
who receive pegfilgrastim from cycle
1 experience a low incidence of
neutropenic events, similar to those
receiving pegfilgrastim in controlled
trials
to compare efficacy and safety of
filgrastim and empegfilgrastim at 3
mg and 6 mg doses
pegfilgrastim
35
open-label
balugrastim (50, 150,
300 and 450 mg/kg) 14
days prior to
chemotherapy
pegfilgrastim (6mg) 24hr
after chemotherapy
13
open-label
pilot phase
empegfilgrastim (3 or 6
mg)
filgrastim 5 mg/kg daily
until ANC recovery (max
14D)
RCT
phase 2
to evaluate the safety and efficacy of
a single fixed dose of pegfilgrastim
per cycle of chemotherapy,
compared with daily administration
of filgrastim, in the provision of
neutrophil support
efficacy of pegfilgrastim compared
with filgrastim or lenograstim in
reducing the incidence of febrile
pegfilgrastim (6 mg)
filgrastim (5 mg/kg)
60
(randomized)
41
empegfilgrasti
m
19
pegfilgrastim
71 (analyzed)
28
pegfilgrastim
118: 88
received daily
G-CSF and 30
singlecentre, open
label
pegfilgrastim
filgrastim
lenograstim
open-label,
single-arm,
phase 4,
communitybased
RCT
neutropenia
Tfayli, A.
(2006)
Trudeau
(2010)
Viens, P.
(2002)
Anticancer
Research (26
(6 C):49114916)
JCO ASCO
(28:15s, 2010
(suppl; abstr
629))
JCO (20:24-36)
Vogel, C. L.
(2005)
received
pegfilgrastim
breast
epirubicin and
docetaxel
efficacy of epirubicin and docetaxel
as neoadjuvant therapy for women
with breast
pegfilgrastim
18 enrolled
breast
epirubicin and
docetaxel
to determine the clinical response
rate
pegfilgrastim
evaluate the safety,
pharmacokinetics, and efficacy of
three different dose levels of
pegylated granulocyte colonystimulating factor (Ro 25-8315) on
progenitor cell mobilization and
hematologic recovery in cancer
patients
percentage of patients developing
febrile neutropenia
Ro 25-8315 (20μg/kg,
60μg/kg, 100μg/kg)
filgrastim (10μg/kg/day,
5μg/kg/day)
93 (enrolled)
All patients
treated with
pegfilgrastim
28 R0 25-8315
8 filgrastim
pegfilgrastim (6mg) D2
placebo D2
463
pegfilgrastim
465 placebo
efficacy and safety of balugrastim
compared with pegfilgrastim in
patients with breast who are
receiving chemotherapy
pegfilgrastim (6mg)
balugrastim (40mg)
304
balugrastim
40 mg (n=153)
pegfilgrastim
6 mg (n=151)
assess the tolerance of
chemotherapy in older women with
breast and determine patterns of
toxicity
pegfilgrastim
62
breast
breast
docetaxel
AT
Volovat, C.
D. (2012)
JCO ASCO
(30(15 SUPPL.
1))
breast
Garg, P.
(2009)
Breast Journal
(15 (4):404408)
breast (1-2)
single
institution,
single arm,
phase 2
phase 1/2
prospective
randomised,
controlled
randomised
multicentre,
double-blind,
placebocontrolled
phase 3
study
double-blind,
randomised,
activecomparator,
noninferiority
trial
retrospective
Burstein, H.
J. (2005)
JCO (23
(33):83408347)
breast (1-3)
doxorubicin,
cyclophosphamide,
paclitaxel
Schwartzber
g, L. S.
(2009)
JCO ASCO (27
(15 SUPPL.
1):e14500)
breast (1-3a)
TAC
Natoli, C.
(2007)
Annals of
Oncology (18
(6):10151020)
breast (2, 3a)
epirubicin,
cyclophosphamide,
docetaxel,
capecitabine
Fagnani, D.
(2011)
European
Journal of
Cancer
(47:S243.)
breast (229,
37% patients)
lung (102, 16%
patients)
lymphomas
(71, 11%
patients)
remaining
36%
breast (2-3)
BurdetteRadoux, S.
(2007)
Khong
(2011)
JCO ASCO (29:
2011 (suppl;
abstr e11519))
breast (2-3)
docetaxel,
epirubicin,
cyclophosphamide
(TEC)
NAC
efficacy of pegfilgrastim and
darbepoetin alfa as hematopoietic
support for dose-dense every-2week adjuvant breast chemotherapy
efficacy of Maxy-G34, a novel potent,
long-acting Pegylated G-CSF vs
pegfilgrastim for the treatment of
chemotherapy induced neutropenia
pegfilgrastim (6mg) D2
Darbepoetin alfa (200ug)
(increases red blood cell
count) every 2 weeks
pegfilgrastim (6mg)
Maxy-G34 (10μg/kg,
30μg/kg, 45μg/kg,
60μg/kg, 100μg/kg) all
24hrs after
chemotherapy
135
open-label
35
Maxy-G34
10μg/kg: 6
30μg/kg: 6
45μg/kg: 6
60μg/kg: 6
100μg/kg: 3
pegfilgrastim
6mg: 8
44 enrolled,
41 assessable
open-label
determine the Incidence of
pathologic complete response
defined as the absence of invasive or
in situ cancer in the breast and the
axillary nodes at definitive surgery
evaluate patterns of use of
pegfilgrastim and
filgrastim/lenograstim in clinical
practice
pegfilgrastim
pegfilgrastim
filgrastim lenograstim
622 (total)
cohort
safety and feasibility of dose-dense
docetaxel/epirubicin/cyclophospham
ide (TEC) in stage 2 and 3 breast
pegfilgrastim (6mg) D2
15, 14
evaluable
open-label,
phase 1/2
to assess the safety of nab-paclitaxel
replacing docetaxel in the
conventional TAC regimen
pegfilgrastim 24hr after
chemotherapy (D9)
16 (enrolled)
All patients
treated with
pegfilgrastim
phase 1
prospective
open-label,
phase 2
Masuda, N.
(2011)
Schwartzber
g, L. (2005)
Gladkov, O.
(2013)
European
Journal of
Cancer
(47:S380)
Journal of
Supportive
Oncology (3 (2
SUPPL. 1):3637)
breast (2-3)
Haematologic
a (EHA)
Holmes, F.
A. (2002)
Freyer, G.
(2013)
Ozer, H.
(2007)
Anticancer
Research (33
(1):301-308)
breast (2-3)
doxetaxel,
doxorubicin,
cyclophosphamide
(TAC)
AC
efficacy and safety of KRN125
(pegfilgrastim) and determine the
optimal dose in breast patients
receiving TAC
evaluate changes in absolute
neutrophil counts and haemoglobin
levels during dose-dense
chemotherapy in patients with
operable breast
pegfilgrastim (1.8mg)
pegfilgrastim (3.6mg)
pegfilgrastim (6.0mg) all
D2
pegfilgrastim
breast (2-4)
AT
to present secondary data on the
incidence of hospitalization and
density and intensity of
chemotherapy in lipegfilgrastim- and
pegfilgrastim-treated patients
lipegfilgrastim (6mg) D2
pegfilgrastim (6mg) D2
breast (2-4)
AT
determine whether a single
subcutaneous injection of
pegfilgrastim is as safe and effective
as daily filgrastim for reducing
neutropenia in patients who
received four cycles of
myelosuppressive chemotherapy
describe prophylactic strategies
[cycle delay, dose-reduction, (G-CSF)
prescription] to prevent recurrence
of neutropenic events (NE) in
patients with solid tumours, and
identify potential predictive factors
of NE recurrence
determine impact of first and
subsequent cycle pegfilgrastim on
pegfilgrastim (100μg/kg)
D2
filgrastim (5μg/kg/d)
from D2
breast (40% of
patients), solid
tumours (53%
of patients)
(metastatic)
breast (46%),
lung (16%),
90 enrolled,
87
administered
multi-centre,
randomised,
phase 2
73 enrolled
58 patients
received 8
cycles, 7
patients
received 5–7
cycles
8 patients
received 2–4
cycles
202
(randomized)
101
lipegfilgrastim
101
pegfilgrastim
310 (total)
retrospective
chart
analysis
pegfilgrastim
548
prospective,
multicentre
and
observationa
l
pegfilgrastim (6mg) D2
2,112
prospective,
community-
RCT
phase 3
multicentre,
randomised,
double-blind,
activecontrol
lymphoma
(18%), ovarian
(8%)
breast
(47.4%), lung
(26.3%), other
location
(26.3%) (3
(36.8%), 4
(63.2%))
breast (axillary
node positive,
nonmetastatic
)
neutropenic events in patients
receiving myelosuppressive
chemotherapy in community
practice: Final results
examined use patterns of
pegfilgrastim in community
according to ESMO and ASCO
evidence-based recommendations
Valera
Rubio, M.
(2011)
JCO ASCO
(29(15 SUPPL.
1))
Puhalla, S.
(2008)
JCO (26
(10):16911697)
Kotasek
(2011)
JCO ASCO (29:
(suppl; abstr
1101))
breast (Early
stage)
TC (docetaxel
cyclophosphamide)
Drullinsky,
P. (2010)
Clinical breast
(10 (6):440444)
breast (early)
cyclophosphamide,
methotrexate,
fluorouracil (CMF)
Jones, R. L.
(2009)
British Journal
of Cancer (100
(2):305-310)
breast (early)
AC, epirubicin
TAC
test the hypothesize that
administering the taxane before the
anthracycline combination would be
associated with fewer dose
reductions and delays than the
reverse sequence in axillary node
positive, nonmetastatic breast
to investigate the frequency of
febrile neutropenia in consecutive
patients treated with TC in a
community practice setting of
predominantly high socio-economic
class, fit patients, and examined the
effect of primary prophylaxis with
pegfilgrastim
tolerability and feasibility of dosedense adjuvant CMF at 14-day
intervals with PEG-filgrastim support
in early stage breast
efficacy of doxorubicin and
cyclophosphamide (AC) or epirubicin
and cyclophosphamide (EC) given 2
weekly with pegfilgrastim
(accelerated) vs 3 weekly (standard)
for women with early breast
based
pegfilgrastim
38 patients
(55.3%
women)
retrospective
analysis of
prescription
pegfilgrastim (6mg) D2
56
randomised,
phase 2,
multicentre
pegfilgrastim
no treatment
74 (treated)
21
pegfilgrastim
Unclear
pegfilgrastim D2
29/38
completed
regimen
open-label
pegfilgrastim
no treatment
126 total, 65
received
pegfilgrastim
randomised,
phase 2
Kahan, Z.
(2008)
Breast
Research and
Treatment
(112 (3):557563)
JCO ASCO
(29(15 SUPPL.
1))
breast (early)
FEC
Feasibility of two dose-dense FEC
regimens with growth factor support
for adjuvant therapy in patients with
early breast
pegfilgrastim (6mg) D2
breast (early)
TC
pegfilgrastim
74
observationa
l, community
practice
Leung, M.
(2012)
JCO ASCO
(30(15 SUPPL.
1))
breast (early)
pegfilgrastim (6mg) D2
filgrastim (300ug) 7-8D
24hr after chemotherapy
140 enrolled
prospective,
observationa
l
Mates, M.
(2012)
Journal of
Clinical
Oncology.
Conference
(30(15 SUPPL.
1))
Medical
Oncology (29
(3):14951501)
Breast
Research and
Treatment
(130 (3):825831)
breast (early)
taxane containing
regimens with or
without
anthracyclines
investigate frequency of febrile
neutropenia in consecutive early
breast patients, and examine effect
of primary prophylaxis with
pegfilgrastim
comparison of incidence & severity
of muscle and/or joint pain in
patients receiving pegfilgrastim (6mg
SC for 1 day) or fixed-dose filgrastim
(300mcg SC for 7-8 days) initiated 24
hours after chemotherapy
Impact of G-CSF on reducing febrile
neutropenia in early stage breast
patients
pegfilgrastim
filgrastim
No treatment
239
Retrospectiv
e
breast (early)
docetaxel and
cyclophosphamide
(TC)
review of institutional experience
with ppGCSF and the TC regimen
pegfilgrastim (6mg) D3
111 enrolled,
95 completed
study
retrospective
breast (early)
doxorubicin,
cyclophosphamide,
paclitaxel
pegfilgrastim
197
randomised
Breast
Research and
Treatment
(125 (1):115-
breast (early)
doxorubicin plus
cyclophosphamide
(AC)
safety of dose-dense doxorubicin
and cyclophosphamide followed by
dose-dense albumin-bound
paclitaxel plus bevacizumab as
adjuvant therapy in patients with
early stage breast
evaluate safety of adjuvant dosedense doxorubicin (A) plus
cyclophosphamide (C) followed by
dose-dense nab-paclitaxel for early-
pegfilgrastim
29 enrolled,
27 completed
open-label
Kotasek, D.
(2011)
Ngamphaib
oon, N.
(2012)
Pippen, J.
(2011)
Robert, N.
(2011)
randomised
120)
stage breast.
Schneeweis
s, A. (2005)
Anti-Cancer
Drugs
(16(9):1023-8)
breast (early)
gemcitabine,
epirubicin,
docetaxel
Staudigl, C.
(2012)
European
Journal of
Cancer
(48:S15.)
breast
Research and
Treatment
(115 (3):609612)
breast (early)
epirubicin,
cyclophosphamide
(EC) followed by
docetaxel
AC, paclitaxel
Sugarman,
S. (2009)
Wenzel, C.
(2005)
breast (early)
breast (early)
epidoxorubicin,
docetaxel and
capecitabine
Anton, A.
(2009)
Annals of
Oncology (20
(3):454-459)
breast (HER-2
overexpressio
n) (2, 3a)
LD, docetaxel
Anton, A.
(2011)
Annals of
Oncology (22
(1):74-79)
breast (HER-2
overexpressio
n) (2, 3a)
liposomeencapsulated
doxorubicin citrate
(LD) and docetaxel
define the maximum tolerated dose
(MTD), efficacy and tolerability of
preoperative gemcitabine plus
epirubicin for 5 cycles followed by 4
cycles of docetaxel given on day 1
every 2 weeks with pegfilgrastim
support
comparison of neutropenia rates in
86 patients who received sequential
anthracyclines and taxanes
pegfilgrastim
50
open-label,
phase 1/2
pegfilgrastim
filgrastim
no treatment
86 (total)
retrospective
chart review
efficacy of pegfilgrastim support in
dose-dense sequential
chemotherapy with doxorubicin and
cyclophosphamide (AC) followed by
paclitaxel (P)
evaluate the safety and activity
profile of epidoxorubicin, docetaxel
and oral capecitabine plus
pegfilgrastim (TEX + P) as
preoperative first-line treatment for
patients with breast
establish the dose-limiting toxicity
(DLT) and the maximum tolerated
dose (MTD) of the combination of
liposome-encapsulated doxorubicin
citrate (LD) and docetaxel in breast
patients, phase 1 clinical trial
efficacy of the combination of
liposome-encapsulated doxorubicin
citrate (LD) and docetaxel in breast
patients, phase 2 clinical trial
pegfilgrastim
59 planned
enrolled
15 evaluated
open-label
pegfilgrastim (6mg) D2
11 enrolled
open-label
pegfilgrastim
20 enrolled,
18 assessable
for DLT
prospective,
open-label,
phase 1
pegfilgrastim
59 enrolled
prospective,
open-label,
phase 2
Dang, C.
(2008)
JCO (26
(8):12161222)
breast (HER2/neu
overexpressed
/amplified)
AC, paclitaxel
Romieu, G.
(2007)
Critical
Reviews in
Oncology/He
matology
((1):64-72)
breast (high
risk 2-3)
FEC100
Wildiers, H.
(2009)
Breast
Research and
Treatment
(114 (1):103112)
breast (high
risk primary
operable)
fluorouracil,
epirubicin and
cyclophosphamide
(FEC) and docetaxel
Bondarenko
, I. (2012)
JCO ASCO
(30(15 SUPPL.
1))
breast (highrisk stage 2-4)
AT
Gladkov, O.
(2012)
Ann Oncol
ESMO
(1548PD)
breast (highrisk stage 2-4)
Skarlos, D.
V. (2009)
Oncology (77
(2):107-112)
breast (highrisk, early)
safety of dose-dense doxorubicin
and cyclophosphamide followed by
paclitaxel with trastuzumab in HER2/neu overexpressed/amplified
breast
determine whether delivery of FEC100 is feasible with pegfilgrastim
support in elderly breast patients
pegfilgrastim (6mg) D2
70 enrolled
open-label,
pegfilgrastim (6mg) D2
primary prophylaxis
(proactive)
pegfilgrastim (6mg)
secondary prophylaxis
(reactive)
pegfilgrastim D2
pegfilgrastim secondary
prophylaxis (reactive)
60
randomised,
phase 2
117
randomised
lipegfilgrastim (6mg) D2
pegfilgrastim (6mg) D2
202
lipegfilgrastim
: 101
pegfilgrastim:
101
to compare the efficacy and safety of
lipegfilgrastim with pegfilgrastim,
particularly with respect to the
absolute neutrophil count
lipegfilgrastim (6 mg) D2
pegfilgrastim (6mg) D2
1) evaluate the rate of febrile
neutropenia in patients with highrisk early breast receiving dosedense chemotherapy
2) evaluate the rate of severe
neutropenia, treatment delays and
pegfilgrastim (6mg) D1
filgrastim D2-10
202
(randomized)
101
lipegfilgrastim
101
pegfilgrastim
214
107 patients
in both groups
(pegfilgrastim
and filgrastim)
double-blind,
randomised,
activecontrolled,
noninferiority
trial
RCT
phase 3
impact of dose densification and
altering sequence of fluorouracil,
epirubicin and cyclophosphamide
[FEC] and docetaxel [Doc] on dose
delivery and tolerability of adjuvant
chemotherapy in breast patients
compare the efficacy and safety of
lipegfilgrastim and pegfilgrastim in
chemotherapy-naive patients with
breast cancer
no
andomised
matched
case-control
study
dose reductions
Livi, L.
(2006)
Anti-Cancer
Drugs (17
(9):10811085)
Clinical breast
(10 (5):36737)
breast (locally
advanced)
vinorelbine,
epirubicin
breast (locally
advanced)
gemcitabine,
epirubicin, and
albumin-bound
paclitaxel
Ramaekers,
R. C. (2012)
JCO ASCO
(30(15 SUPPL.
1).)
breast (N=16),
colorectal
(N=7), head
and neck
(N=1), NHL
(N=1), NSCLC
(N=1)
Piedbois, P.
(2007)
Annals of
Oncology (18
(1):52-57)
breast (node
positive
invasive
breast
adenocarcino
ma)
anthracycline
(N=9), taxane
(N=7), 5FU/oxaliplatin
(N=7), 5FU/cisplatin (N=1),
gemcitabine/oxalipl
atin (N=1),
pemetrexed/carbo
platin (N=1)
TEC
Rossi, L.
(2012)
European
Journal of
Cancer
breast (nonmetastatic)
Yardley, D.
(2010)
FEC100
5-fluorouracil,
epirubicin,
efficacy of alternating intravenous
and oral vinorelbine plus epirubicin
with pegfilgrastim as neoadjuvant
treatment of locally advanced breast
increase efficacy and decrease
toxicity of a 3-drug gemcitabinecontaining neoadjuvant regimen by
administering dose-dense therapy
with pegfilgrastim, and including
albumin-bound paclitaxel as the
taxane
efficacy and safety of half-dose
pegfilgrastim in general oncology pts
on cytotoxic chemotherapy at St
Francis Cancer Centre
pegfilgrastim (6mg) D2
22 enrolled
open-label
pegfilgrastim (6mg) D2
123
multi-centre,
phase 2
pegfilgrastim (6mg)
pegfilgrastim half-dose
(3mg)
26
single centre,
open-label
determine optimal dose and
schedule of chemotherapy in nodepositive breast: Docetaxel followed
by epirubicin/cyclophosphamide
(T/EC), or the reverse sequence
(EC/T), every 2 weeks, versus
docetaxel, epirubicin and
cyclophosphamide (TEC) every 3
weeks. AERO B03 randomized phase
2 study
efficacy, safety profiles and costeffectiveness analysis of
pegfilgrastim and lenograstim in
pegfilgrastim
99
randomised,
phase 2
pegfilgrastim (6mg) D2
lenograstim (263μg) D510
20 enrolled
8
pegfilgrastim
prospective
(48:S154)
Papa, A.
(2012)
Loibl, S.
(2011)
Dang, C.
(2008)
JCO ASCO
(30(15 SUPPL.
1)), Support
Care Cancer
MASCC (20
(Suppl 1):S1–
S283)
Supportive
Care in Cancer
(19 (11):17891795)
breast (nonmetastatic)
FEC100 TAC
breast
(primary,
node positive)
epirubicinpaclitaxelcyclophosphamide
Clinical breast
(8 (5):418424)
breast
(resectable)
epirubicin,
cyclophosphamide,
paclitaxel
breast (T2-T4)
chondrosarco
ma, EWS, OS
(recurrent
(EWS),
von
Minckwitz,
G. (2008)
Fox, E.
(2012)
cyclophosphamide
(FEC 100)
Oncologist (17
(3):321)
patients with non-metastatic breast
receiving adjuvant myelosuppressive
chemotherapy
efficacy, safety, and costeffectiveness analysis of
pegfilgrastim and lenograstim in
patients with nonmetastatic breast
receiving myelosuppressive
chemotherapy
12
lenograstim
pegfilgrastim (6mg) D2
lenograstim (263 μg) D510
50 (analyzed)
28
lenograstim
22
pegfilgrastim
retrospective
comparison of pegfilgrastim on day 2
vs. day 4 as primary prophylaxis of
intense dose-dense chemotherapy in
patients with node-positive primary
breast
feasibility of prolonged dose-dense
epirubicin and cyclophosphamide
followed by paclitaxel in breast
pegfilgrastim D2
pegfilgrastim D4
351
P2 (n=174)
versus P4
(n=177)
Randomised
controlled
trial,
multicentre
pegfilgrastim (6mg) D2
open-label
pilot phase
TAC
compared the efficacies of four
regimens for primary prophylaxis of
FN and related toxic effects in breast
patients receiving neoadjuvant TAC
pegfilgrastim (6mg) D2
filgrastim (5μg/kg/d) D510
lenograstim
(150μg/m2/d) D5-10
gemcitabine,
docetaxel
determine the objective response
rate using Response Evaluation
Criteria in Solid Tumours (RECIST)
pegfilgrastim
filgrastim
38 enrolled
33 (87%)
completed
regimen as
planned
ciprofloxacin
D5-14 (n =
253)
daily G-CSF
D5-10 (n =
377)
pegfilgrastim
D2 (n = 305)
pegfilgrastim
plus
ciprofloxacin
(n = 321)
53 enrolled, 7
withdrew
open-label,
observation
open-label,
phase 2
unresectable
or recurrent
(OS))
colorectal
Hecht, J. R.
(2010)
Clinical
Colorectal
Cancer (9
(2):95-101)
evaluate reduction of neutropenia
and febrile neutropenia in patients
with colorectal cancer receiving
pegfilgrastim with every-2-week
chemotherapy
to determine reported incidences of
febrile neutropenia, AEs, and SAEs
in North America (NA) vs rest of
world (ROW)
pegfilgrastim (6mg) D4
placebo D4
241
placebo: 118
pegfilgrastim:
123
randomised,
placebocontrolled
phase 3
Decaestecke
r (2013)
Support Care
Cancer MASCC
(DOI
10.1007/s005
20-013-17983)
JCO ASCO (31,
(suppl; abstr
3575))
colorectal
(locallyadvanced or
metastatic)
bevacizumab and
FOLFOX or FOLFIRI
pegfilgrastim (6mg)
placebo
845
(randomized)
422
pegfilgrastim
423 placebo
RCT
phase 3
colorectal
(locallyadvanced or
metastatic)
FOLFOX/B or
FOLFIRI/B
to evaluate the efficacy of
pegfilgrastim in reducing the
incidence of febrile neutropenia
pegfilgrastim (6 mg)
placebo
24hr after chemotherapy
RCT
phase 3
CRPC
(metastatic
progressive)
ixabepilone,
mitoxantrone
pegfilgrastim
JCO ASCO
(30(5 SUPPL.
1))
CRPC
(metastatic)
docetaxel
pegfilgrastim D2
47 enrolled
prospective
open-label,
phase 2
Adesunloye,
B. (2012)
JCO ASCO
(30(15 SUPPL.
1))
CRPC
(metastatic)
docetaxel
pegfilgrastim D2
54 enrolled
prospective
open-label,
phase 2
Huang, X.
(2011)
JCO ASCO
(29(7 SUPPL.
CRPC
(metastatic)
docetaxel
efficacy of ixabepilone,
mitoxantrone, and prednisone for
metastatic castration-resistant
prostate cancer after docetaxelbased therapy
safety/efficacy of lenalidomide in
conjunction with bevacizumab,
docetaxel and prednisone for
treatment of mCRPC
safety/efficacy of lenalidomide in
conjunction with bevacizumab,
docetaxel and prednisone for
treatment of mCRPC
efficacy of bevacizumab (A),
lenalidomide (R), docetaxel (D), and
845
(randomized)
783
(completed
treatment)
422
pegfilgrastim
56
Harzstark,
A. L. (2011)
Cancer (117
(11):24192425)
Adesunloye,
B. (2012)
pegfilgrastim
28/51
open-label,
phase 2
Pinter
(2013)
fluouracil,
irinotecan,
oxaliplatin
multicentre,
observationa
l, phase 2
1))
Rosenberg,
J. E. (2009)
JCO ASCO (27
(17):27722778)
CRPC
(metastatic)
ixabepilone,
mitoxantrone
Chiesa
(2010)
JCO ASCO
(28:15s, 2010
(suppl; abstr
4142))
JCO ASCO (30,
2012 (suppl;
abstr 4097))
Cancer
Chemotherap
y and
Pharmacology
(67 (1):41-48)
Tumori (96
(1):48-53)
gastric
docetaxel, cisplatin,
and 5-fluorouracil
(TCF-dd)
gastric (locally
advanced or
metastatic)
gastric
(metastatic)
TCF-dd, oxaliplatin,
5-fluorouracil, and
irinotecan (COFFI)
TCF-dd COFFI
gastric
(metastatic)
docetaxel, cisplatin,
followed by 5fluorouracil
JCO ASCO (31,
2013 (suppl;
abstr e15086))
JCO ASCO (31,
2013 (suppl;
abstr 4112))
gastric
(metastatic)
TCF-dd
gastroesophag
eal
TCF-dd
Japanese
Journal of
lung
Tomasello,
G. (2012)
Dalla
Chiesa, M.
(2011)
Tomasello,
G. (2010)
Tomasello,
G. (2013)
Toppo
(2013)
Yamamoto,
N. (2009)
prednisone (P) in patients with
metastatic castration-resistant
prostate cancer (mCRPC)
determine safety of ixabepilone,
mitoxantrone, and prednisone in
patients with metastatic castrationresistant prostate cancer previously
treated with docetaxel-based
therapy
to update a larger case series
pegfilgrastim D2
36
multi-centre,
open-label,
phase 1
pegfilgrastim (6mg) D3
68 enrolled
Case series
phase 2
to evaluate this therapeutic
approach in a larger case series
pegfilgrastim (6mg) D3
43 (74% male)
40 evaluable
Case series
evaluate a new strategy of two
sequential, intensified chemotherapy
regimens in metastatic gastric cancer
pegfilgrastim (6mg) D3
open-label,
phase 2
feasibility and activity of an
intensified dose-dense TCF regimen
(q2w) modifying the 5-fluorouracil
infusion with l-folinic acid/5fluorouracil according to the "De
Gramont regimen"
to assess the efficacy and safety of
high activity of a dose-dense TCF
regimen in elderly patietns
to investigate the efficacy and safety
of this intensified dose-dense
regimen in a single-center large
cohort of patients
investigate the safety,
pharmacokinetic and
pegfilgrastim (6mg) D3
40 enrolled,
23 proceeded
to second
treatment
regimen
32 enrolled
(63% male,
37% female)
pegfilgrastim (6mg) D3
119 (analyzed)
Retrospectiv
e
pegfilgrastim (6mg) D3
every 14 days
128 (analyzed)
Unclear
pegfilgrastim 30 μg/kg
pegfilgrastim 60 μg/kg
18, 6 in each
group
sequentially
enrolled
open-label
Clinical
Oncology (39
(7):425-430)
Shipley, D.
(2012)
JCO ASCO (30,
2012 (suppl;
abstr 7100))
lung
(extensive
stage)
amrubicin and
carboplatin
Mancini
(2012)
Ann Oncol
ESMO (1004P)
MMMT (2-4)
Johnston, E.
(2000)
JCO (18
(13):25222528)
Cancer
Investigation
(23(7):573-6)
NSCLC
Cisplatinifosfamide or
carboplatinpaclitaxel
carboplatin and
paclitaxel.
Lung Cancer
(53 (3):347353)
Miller, A. A.
(2008)
NSCLC ( locally
advanced and
metastatic 34)
NSCLC (3B
(effusion), 4)
Udo (2012)
NSCLC (3b, 4)
Lokich, J.
(2005)
Raez, L. E.
(2006)
NSCLC
taxane, cisplatin,
irinotecan,
gemcitabine,
cisplatin,
vinorelbine,
carboplatin
docetaxel,
oxaliplatin
docetaxel, cisplatin
Cisplatin/etoposide
pharmacodynamic profiles of
pegfilgrastim (KRN125), a long-acting
granulocyte colony-stimulating
factor, in lung cancer patients with
chemotherapy-induced neutropenia
to evaluate amrubicin and
carboplatin in newly diagnosed ESSCLC
pegfilgrastim 100 μg/kg
to evaluate two different
chemotherapy combinations in
terms of toxicity and oncologic
outcome
efficacy of SD/01 (pegfilgrastim) Vs.
filgrastim in patients receiving
chemotherapy
safety and efficacy on administering
pegfilgrastim on the same day as
chemotherapy
pegfilgrastim
no treatment
pegfilgrastim (6mg) D4
78 (enrolled)
All patients
treated with
pegfilgrastim
24 (enrolled)
10
pegfilgrastim
prospective,
phase 2
pegfilgrastim
daily G-CSF
13 (total)
randomised
pegfilgrastim (30, 100, or
300 μg/kg)
filgrastim (5 μg/kg/d)
80
open-label
efficacy and safety of oxaliplatin and
docetaxel in patients with locally
advanced and metastatic non-smallcell lung cancer (NSCLC)
feasibility and safety of dose-dense
docetaxel and cisplatin regimen
with/without BNP7787 in non-small
cell lung cancer
pegfilgrastim D1
29 treated, 27
evaluable
open-label,
phase 2
pegfilgrastim 6mg D2
randomised,
phase 2
to evaluate the efficacy and safety of
lipegfilgrastim
lipegfilgrastim 6 mg D4
placebo
160 patients
enrolled, 5
never started
therapy and 4
were ineligible
375
(randomized)
250
lipegfilgrastim
125 placebo
Case control
RCT
Riedel, R. F.
(2007)
Journal of
Thoracic
Oncology:
Official
Publication of
the
International
Association
for the Study
of Lung
Cancer
(2(6):520-5)
Stinchcomb
e, T. E.
(2008)
Tiersten
(2009)
Monk, B. J.
(2011)
Schuman, S.
I. (2009)
JCO ASCO
(27:15s, 2009
(suppl; abstr
5544))
Gynecologic
Oncology (120
(3):459-463)
The journal of
supportive
oncology
(7(6):225-8)
NSCLC (locally
advanced or
metastatic)
carboplatin,
vinorelbine
efficacy of carboplatin/vinorelbine
with pegfilgrastim support for the
treatment of patients with advanced
non-small cell lung cancer
pegfilgrastim 6mg D9
30 enrolled
open-label,
phase 2
NSCLC
(unresectable
3a, 3b
52% female,
61% stage 3a)
carboplatin,
irinotecan,
paclitaxel
with 3-dimensional
TCRT
(radiotherapy)
tolerability of gefitinib in combined
modality therapy in combination
with three-dimensional thoracic
conformal radiation therapy (3dimensional TCRT)
pegfilgrastim
open-label
ovarian (3-4)
carboplatin and
paclitaxel
to investigate the feasibility of dosedense CP for women with ovarian
cancer
pegfilgrastim (6mg) D2
ovarian,
peritoneal
(persistent
(ovarian)
primary
(peritoneal))
ovarian,
primary
peritoneal
35 (76%)
epithelial
docetaxel,
trabectedin
estimate the activity of docetaxel
over 1 h followed by trabectedin
over 3 h with filgrastim,
pegfilgrastim, or sargramostim every
3 weeks (one cycle)
pegfilgrastim
filgrastim
sargramostim
23
21 initiated
the
concurrent
chemoradiatio
n, 20 patients
completed
therapy to 74
Gy
43 (enrolled)
All patients
treated with
pegfilgrastim
71 (total)
safety of pegfilgrastim on same day
as myelosuppressive chemotherapy
for ovarian or primary peritoneal
cancer
pegfilgrastim 1 hour
post-chemotherapy
46
singleinstitution,
retrospective
feasibility,
phase 1
two-stage
Tiersten, A.
D. (2010)
Gynecologic
Oncology (118
(3):303-307)
Gunturu
(2012)
JCO ASCO (30,
2012 (suppl;
abstr e14534))
Mahaseth,
H. (2012)
ovarian, 6
(13%) primary
peritoneal,
and 5 (11.0%)
ovarian germ
cell or stromal
cell carcinoma
ovarian, tubal,
primary
peritoneal
(untreated 34)
carboplatin/paclita
xel
feasibility study in patients with
untreated Stage 3 and 4 ovarian,
tubal or primary peritoneal cancer
pegfilgrastim (6mg) D2
pancreatic
cancer
FOLFIRINOX
pegfilgrastim
JCO ASCO (30,
2012 (suppl;
abstr e14614))
pancreatic
cancer
mFOLFIRINOX
Gunturu, K.
S. (2012)
Journal of
Clinical
Oncology.
Conference
(30(4 SUPPL.
1))
fluorouracil,
irinotecan,
oxaliplatin
(FOLFIRINOX)
Adesunloye,
B. (2012)
JCO ASCO (30,
2012 (suppl;
abstr 4569))
pancreatic
cancer (locally
advanced
unresectable
(LAPC), and
metastatic
(MPC))
prostate
cancer
to assess the impact of dose
attenuations on toxicity and efficacy,
we reviewed our experience with
FOLFIRINOX in advanced PC pts
to assess efficacy and safety of
mFOLFIRINOX in patients with locally
advanced or metastatic pancreatic
cancer.
assess the impact of dose
attenuations on FOLFIRINOX toxicity
and efficacy with advanced
pancreatic cancer
pegfilgrastim D2
Karzai
(2013)
JCO ASCO (31,
2013 (suppl;
abstr e16017))
to assess the efficacy and safety of
dual antiangiogenic therapy using
lenalidomide and bevacizumab with
docetaxel and prednisone
to compare and contrast our study
combining lenalidomide (L), with
bevacizumab (B), docetaxel (D), and
prednisone (P) (ART-P) in mCRPC
prostate
cancer
bevacizumab and
thalidomide,
docetaxel and
prednisone
ART-P
pegfilgrastim (6mg) Q2W
pegfilgrastim
pegfilgrastim D2
43 patients
enrolled
31 patients
completed 6
or more cycles
of therapy
35 (treated)
All patients
treated with
pegfilgrastim
28 (analyzed)
All patients
treated with
pegfilgrastim
31
open-label,
phase 1
54 (enrolled)
All patients
treated with
pegfilgrastim
63 (included)
All patients
treated with
pegfilgrastim
prospective
open-label
Retrospectiv
e
Retrospectiv
e
retrospective
Unclear
with these failed phase 3 trials
Small (2009)
JCO ASCO
(27:15s, 2009
(suppl; abstr
5058))
prostate
cancer
ixabepilone,
mitoxantrone, and
prednisone
Not stated
pegfilgrastim (6mg) D2
Fox, E.
(2009)
sarcomas
vincristine,
doxorubicin, and
cyclophosphamide
(VDC), etoposide
and ifosfamide (IE)
pegfilgrastim (100ug/kg)
filgrastim (5ug/kg/d)
Nagel, S.
(2011)
SCLC
carboplatin,
etoposide
Pirker, R.
(2006)
SCLC
doxorubicin,
cyclophosphamide,
etoposide (ACE)
compare effectiveness, tolerance,
and pharmacokinetics of a single
dose of pegfilgrastim to daily
filgrastim in children and young
adults with sarcomas treated with
dose-intensive combination
chemotherapy
feasibility, efficacy, and safety of the
administration of darbepoetin alfa to
patients with SCLC receiving dosedense (every 2 weeks) standard
chemotherapy
Achieve full-dose, on-schedule
administration of ACE chemotherapy
every 14 days for the treatment of
patients with extensive small-cell
lung cancer
43 (enrolled)
All patients
treated with
pegfilgrastim
34 enrolled,
32 completed
study
pegfilgrastim
pegfilgrastim (6mg) D4
prospective
phase 2
RCT
randomised,
open label,
phase 2
30 patients
with extensive
small cell lung
cancer
admitted into
the study; 27
patients
received
pegfilgrastim
and at least 1
cycle of ACE
14
chemotherapy
, and 17
received all 6
cycles of
ACE 14
chemotherapy
open-label,
nonrandomised
Shipley, D.
(2012)
JCO ASCO
(30(15 suppl
1))
SCLC
(extensive
stage)
amrubicin and
carboplatin
evaluating amrubicin and carboplatin
efficacy in newly diagnosed ES-SCLC
pegfilgrastim (6mg) D4
78 enrolled
56% female.
64%
completed 4
cycles of
treatment
14 (treated)
All patients
treated with
pegfilgrastim
multicentre,
phase 2
Brown
(2009)
JCO ASCO
(27:15s, 2009
(suppl; abstr
3504))
SCLC, other
solid tumors
Obatoclax and
topotecan
to evaluate the safety profile and
maximum tolerated dose (MTD) of
obatoclax plus topotecan in patients
with relapsed SCLC and other solid
tumors
pegfilgrastim D8
Schmitt, T.
(2011)
BMC Cancer
(11(510)), JCO
ASCO
(29(15 suppl;
abstr 10076))
etoposide,
ifosfamide,
doxorubicin (EIA)
evaluating neo-/adjuvant EIA
chemotherapy, surgical resection
and radiotherapy in high-risk soft
tissue sarcoma
AlmenarCubells, D.
(2011)
JCO ASCO
(29(15 SUPPL.
1))
soft tissue
sarcoma
primary
tumours were
located in the
extremities or
trunk (92%),
6% originated
in the
abdomen/retr
operitoneum
(2-3)
solid tumours
(3-4 (81.2% of
patients))
pegfilgrastim (6mg) D5
50 subjects
(male=33,
female=17,
median age
50.1 years)
were enrolled
prospective,
nonrandomised,
phase 2
effectiveness of daily G-CSFs vs PEG
in reducing incidence of neutropenia
and neutropenia-based
hospitilisations
pegfilgrastim
daily G-CSF
pegfilgrastim:
180
daily G-CSF:
211
determine safety, optimally
tolerated regimen (OTR),
pharmacokinetics,
pharmacodynamics, and preliminary
clinical activity of lapatinib and
docetaxel in patients with advanced
pegfilgrastim
52 enrolled
multi-centre,
retrospective
,
observationa
l
open-label,
phase 1
LoRusso, P.
M. (2008)
JCO
(26(18):30516)
solid tumours
(advanced)
doxetaxel
phase 1 dose
escalation
study
solid tumours
Sanborn, S.
L. (2009)
Investigational
New Drugs (27
(5):453-460)
Dragnev, K.
H. (2010)
Brighenti
(2013)
Pagliaro, L.
C. (2011)
Pautier
(2013)
JCO ASCO (31,
2013 (suppl;
abstr
e15502)), Eur
Journal of
Cancer
(47:S516)
JCO ASCO
(29(7 SUPPL.
1))
JCO ASCO (31,
2013 (suppl;
abstr 10505))
solid tumours
(advanced)
docetaxel
efficacy and safety of docetaxel given
every 3 weeks plus daily
lenalidomide in patients with
advanced solid tumours
feasibility of using filgrastim or
pegfilgrastim to increase the dose
intensity of biweekly docetaxel and
gemcitabine
pegfilgrastim D2
33 enrolled
open-label,
phase 1
solid tumours
(metastatic)
gemcitabine,
docetaxel
pegfilgrastim
filgrastim
singleinstitution,
open-label,
phase 1
CGP
Not stated
pegfilgrastim (6mg) D2
35 patients
enrolled
25: filgrastim
10:
pegfilgrastim
35 (analyzed)
All patients
treated with
pegfilgrastim
urothelial
(metastatic)
urothelial
carcinoma
(UC)
(metastatic or
u esectable)
uterine
leiomyosarco
ma (u-LMS),
soft tissue
LMS
(advanced)
gemcitabine,
paclitaxel, and
doxorubicin (GTA)
efficacy of GTA treatment for UC in
pts with renal insufficiency
pegfilgrastim (6mg)
D1/D2
25 enrolled,
21 assessable
open-label ,
multi-centre,
phase 2
doxorubicine,
trabectidine
to determine the disease control
rate
pegfilgrastim (6mg) D2
45 (enrolled)
All patients
treated with
pegfilgrastim
prospective
phase 2
non-myeloid
malignancies
myelosuppressive
chemotherapy
compare patterns of use of daily GCSF and pegfilgrastim, and
Chemotherapy Induced Neutropeniarelated outcomes
pegfilgrastim
daily G-CSF
pegfilgrastim:
75
daily G-CSF:
111
multi-centre,
retrospective
,
observationa
Unclear
Combinatio
n
Almenar, D.
(2009)
European
Journal of
Cancer Care
(18(3):280-6)
l
Henk, H. J.
(2013)
Journal of
Medical
Economics (16
(1):160-168)
Journal of
Medical
Economics (12
(3):203-210)
HL, NHL, solid
tumours
efficacy of pegfilgrastim Vs. filgrastim
Vs. sargramostim in reducing
neutropenia events in NHL
pegfilgrastim
filgrastim
sargramostim
9330 and
8762
lymphomas,
solid tumours
pegfilgrastim
filgrastim
no treatment
3123 (total)
Whitworth,
J. M. (2009)
Gynecologic
Oncology
(112(3):601-4)
pegfilgrastim (6mg) D1
pegfilgrastim (6mg) D2
230
retrospective
Shi, Y. K.
(2006)
Zhonghua yi
xue za zhi (
(48):3414-9)
gynaecologic
malignancies
(3-4 or
recurrent
disease (79%))
breast, NHL,
NSCLC
pegfilgrastim (100μg/kg)
D3
filgrastim (5μg/kg/d) D3
for 14 days or until ANC
recovery
104 enrolled
randomised,
open-label,
match and
cross-over
study
phase 2
Morrison, V.
A. (2007)
Journal of
Managed Care
Pharmacy (13
(4):337-348)
determine if granulocyte-colonystimulating factor (G-CSF) primary
prophylaxis is associated with a
lower risk of febrile neutropenia (FN)
than non-primary prophylaxis
the safety and efficacy of day 1
versus day 2 administration of
pegfilgrastim in patients receiving
myelosuppressive chemotherapy for
gynaecologic malignancies
efficacy and safety of daily
administration of recombinant
human granulocyte colonystimulating factor (rhG-CSF), and a
single subcutaneous injection of
pegylated recombinant human
granulocyte colony-stimulating
factor (PEG-rhG-CSF), in
chemotherapy-induced neutropenia
(1) describe the use of pegfilgrastim
and filgrastim in oncology practices
throughout the United States and (2)
compare their effectiveness in actual
practice as measured by the
outcome of febrile neutropenia in
patients who received chemotherapy
regimens administered every 3 to 4
weeks for breast, lung, ovarian, colon
cancer, or lymphoma and who
received a CSF prior to developing FN
pegfilgrastim
filgrastim
2,863
1,451
(filgrastim)
1,412
(pegfilgrastim)
retrospective
, multicentre 20012003 data,
observationa
l
Hershman,
D. (2009)
breast, colon,
lung,
lymphoma,
ovarian
docetaxel/carbopla
tin (53%)
followed by
paclitaxel/carboplat
in (19%)
retrospective
US claims
database
analyses
retrospective
cohort
Naeim, A.
(2010)
Blood ASH
(116(21))
breast, colon,
lung, NHL,
ovarian,
efficacy of pegfilgrastim vs filgrastim
pegfilgrastim
filgrastim
3,958 (total)
breast (57%),
lung cancer
(18%), and
NHL (17%)
Naeim, A.
(2013)
BMC Cancer
(13(11))
breast, colon,
lung, NHL,
ovarian,
efficacy of pegfilgrastim vs filgrastim
pegfilgrastim
filgrastim
3535 (total)
Tan, H.
(2011)
JCO ASCO
(29(15 SUPPL.
1))
breast,
colorectal,
lung, NHL,
ovarian cancer
breast,
colorectal,
NSCLC (newly
diagnosed)
effectiveness of prophylaxis with GCSFs filgrastim (FIL) and pegfilgrastim
(PEG), and GM-CSF sargramostim
(SAR)
determine the impact of primary
prophylactic colony stimulating
factor (CSF) use on febrile
neutropenia in a large patient
population receiving contemporary
chemotherapy regimens to treat
breast, colorectal cancer, or nonsmall cell lung cancer (NSCLC)
to examine the serum
concentrations of pegfilgrastim
during recovery of absolute
neutrophil count (ANC) in patients
with cancer who received
pegfilgrastim after chemotherapy
pegfilgrastim
filgrastim
sargramostim
only patient
cycles
reported
pegfilgrastim
filgrastim
2728
breast (998
patients)
colorectal
cancer (688
patients)
NSCLC (1042
patients)
370
McCune, J.
S. (2012)
Yang, B. B.
(2007)
Pharmacother
apy (32 (1):719)
breast, HL,
NHL. NSCLC
pegfilgrastim 24hr after
chemotherapy
Linked to
Naeim 2013
retrospective
, multicentre 20042009 data
Linked to
Naeim, 2010
retrospective
, multicentre 20042009 data
retrospective
Retrospectiv
e claims
analysis
retrospective
, pooled
analysis
Data were
pooled from
seven
pegfilgrastim
registrational
clinical trials:
four openlabel phase 1
or 2 studies
Jurczak
(2013)
Tan, H.
(2011),
(2009)
Weycker, D.
(2009)
Support Care
Cancer MASCC
(DOI
10.1007/s005
20-013-17983)
Current
Medical
Research and
Opinion (27
(1):79-86), JCO
ASCO (27:15s,
(suppl; abstr
6626))
Clinical
Therapeutics
(31 (5):10691081)
Wagner, L. I.
(2008)
Balducci, L.
(2007)
Unidentifie
d tumour
type
breast, lung,
lymphoma,
ovarian cancer
(advanced3-4
(76 %))
to determine the most important
reasons contributing to physicians’
decision to use pegfilgrastim primary
prophylaxis in patients with high
overall febrile neutropenia risk
pegfilgrastim
breast, lung,
NHL
1) compare the effectiveness of
prophylactic pegfilgrastim and
filgrastim on the risk of
hospitalizations
2) the secondary objective was to
compare the effectiveness of the
timing of initiation (prophylactic
versus delayed)
compare the risks of hospitalization
for neutropenic complications of
chemotherapy in US clinical practice
in patients with primary solid
tumours receiving pegfilgrastim or
filgrastim prophylaxis
established the psychometric
properties of the Functional
Assessment of Cancer TherapyNeutropenia (FACT-N)
evaluating the application of
pegfilgrastim (proactive vs reactive)
for decreasing incidences of febrile
neutropenia in patients with solid
tumours or NHL
pegfilgrastim
filgrastim
breast, lung,
NHL
breast, lung,
NHL, ovarian
Oncologist (12
(12):14161424)
NHL, solid
tumours
1006
(enrolled)
and three
randomised
phase 2 or 3
studies
Prospective
observationa
l
retrospective
only patient
cycles
reported
(5571)
pegfilgrastim
filgrastim
only cycles
mentioned
retrospective
cohort
pegfilgrastim primary
prophylaxis (proactive)
pegfilgrastim secondary
prophylaxis (reactive)
pegfilgrastim at cycle 1
(proactive)
pegfilgrastim after cycle
1 (reactive)
852
randomised
852 enrolled
RCT
Ho, P.
(2012)
European
Journal of
Haematology
(88 (5):416421)
Green, M.
D. (2003)
ABVD
efficacy of pegfilgrastim and
filgrastim at maintaining dose
intensity after AVBD therapy
complicated by neutropenia
pegfilgrastim
filgrastim
85 (total)
retrospective
AT
efficacy of a single fixed 6 mg dose of
pegfilgrastim per cycle of
chemotherapy, compared with daily
administration of filgrastim, in the
provision of neutrophil support
determine a Phase 2 dose and
schedule of LY2523355 that may be
safely administered to patients with
advanced malignancy
pegfilgrastim (6mg)
filgrastim (5mg/kg)
157 (total)
RCT, phase 3
pegfilgrastim D4
no treatment
46
to determine the Phase 2 dose and
schedule of LY2523355 that can be
safely administered to patients with
advanced malignancies
pegfilgrastim D6
46 (enrolled)
pegfilgrastim
open-label,
multicentre,
dose
escalation
study, phase
1
phase 1 dose
escalation
study
Verschraege
n, C. (2011)
AACR NCI
EORTC (10(11
SUPPL. 1))
(advanced
malignancy)
LY2523355
Shih (2011)
JCO ASCO (29:
2011 (suppl;
abstr 2600))
(advanced
malignancy)
LY2523355
NCT0011476
4
AML (De
novo)
Induction and
consolidation
myelosuppressive
chemotherapy
NCT0083726
5
breast
AT
NCT0112619
0
breast
AT
NCT0151673
6
breast
Myelosuppressive
chemotherapy
NCTs
to determine if a single dose of
pegfilgrastim
pegfilgrastim is able to reduce the
filgrastim
time of severe neutropenia
to determinate of the effect of
Neugranin on the duration and
severity of severe neutropenia
to evaluate the effect of
Neugranin on the duration and
severity of severe neutropenia
to evaluate the efficacy of LAEP2006 compared to Peg-
84 (enrolled)
RCT
pegfilgrastim 6 mg
Neugranin
334
(enrolled)
RCT
pegfilgrastim 6 mg
Neugranin
381
(enrolled)
RCT
pegfilgrastim s.c. post
chemotherapy
302
(estimated
RCT
filgrastim with respect to the
mean duration of severe
neutropenia
NCT0156908
7
breast
Myelosuppressive
chemotherapy
to compare the incidence of
CTCAE grade 3/4 neutropenia
after a single administration of
recombinant human pegylated
filgrastim empegfilgrastim versus
daily administration of filgrastim
for neutropenia prophylaxis
NCT0164832
2
breast
TC (docetaxel +
cyclophosphamid
e)
to evaluate the efficacy and
safety of F-627
NCT0172486
6
breast
TC
to assess the effect of test doses
of HM10460A on the mean
duration of severe neutropenia
Myelosuppressive
chemotherapy
to evaluate the efficacy of LAEP2006 compared to Pegfilgrastim with respect to the
mean duration of severe
neutropenia
FOIL, FOLFOX or
FOLFIRI
to evaluate the safety and
effectiveness of pegfilgrastim in
reducing grade 3/4 neutropenia
when given after one of three
chemotherapy regimens (FOIL,
NCT0173517
5
breast
NCT0009480
9
colorectal
cancer
(locally
advanced or
metastatic)
application
LA-EP2006 s.c. post
chemotherapy
application
empegfilgrastim 3 or 6
mg single
administration
subcutaneously, 24 h
after the
chemotherapy
filgrastim daily (until
ANC 10 000/μL or for
14 days, whichever
occurred first),
starting 24 h after the
chemotherapy
pegfilgrastim
F-627 (80, 240 or 320
µg/kg)
pegfilgrastim 6mg
HM10460A (45, 135 or
270 μg/kg)
pegfilgrastim s.c. post
chemotherapy
application.
LA-EP2006 s.c. post
chemotherapy
application.
pegfilgrastim (6 mg
subcutaneous
injection once per
cycle)
enrolled)
60
(estimated
enrolled)
RCT
200
(estimated
enrolled)
RCT
144
(enrolled)
RCT
302
(estimated
enrolled)
RCT
252
(enrolled)
RCT
FOLFOX or FOLFIRI) in patients
with locally advanced or
metastatic colorectal cancer
NCT0091117
0
NCT0079426
1
NCT0154107
2
colorectal
cancer
(Newly
diagnosed,
locallyadvanced or
metastatic)
FOLFOX or FOLFIR
to evaluate the efficacy of
pegfilgrastim to reduce the
incidence of febrile neutropenia
lymphoma,
myeloma
High-dose
chemotherapy
and autologous
peripheral stem
cell support
to evaluate the efficacy and
tolerance of a single
administration of pegfilgrastim
and to estimate the costs
incurred
NHL (B-cell)
(malignant)
High-dose
chemotherapy
and autologous
peripheral stem
cell
transplantation
to describe the kinetics of
lymphocyte subsets
reconstitution after growth factor
administration
pegfilgrastim 6 mg (24
hrs after
chemotherapy)
placebo (24 hrs after
chemotherapy)
pegfilgrastim 6 mg at
D5
filgrastim 5 µg/kg/day
from D5 until recovery
from aplasia (PNN >
0.5 G/L)
pegfilgrastim single
subcutaneous
administration of
pegfilgrastim, 6 mg at
day 5 (D5) after
autologous stem cell
transplantation
filgrastim daily
subcutaneous
administration,
5µg/kg/day from day 5
(D5) after autologous
stem cell
transplantation until
recovery from aplasia
(Neutrophils >= 0.5
G/L)
847
(enrolled)
RCT
150
(estimated
enrolled)
RCT
60
(estimated
enrolled)
RCT
NCT0011378
9
ovarian
(Relapsed/
refractory)
Multi-day
topotecan
regimen
NCT0000485
3
sarcoma
(Newly
diagnosed)
VDoxC alternating
with
ifosfamide/etopo
side (IE)
NCT0055446
3
SCLC
(Limited
stage
disease)
Cisplatin and
etoposide
18 studies excluded due to lack of chemotherapy and/or tumour data
1 study (Neal, 2010) removed as identical data reported in Traynor, 2011
to assess the safety and efficacy
of pegfilgrastim, in terms of
duration of grade 4 neutropenia
to compare the tolerance,
toxicity, and therapeutic effects
of filgrastim-SD/01 given as a
single injection after
chemotherapy to daily
subcutaneous filgrastim
to evaluate G-CSF and
pegfilgrastim for the treatment of
neutropenia
pegfilgrastim
placebo
21 (enrolled)
RCT
pegfilgrastim
filgrastim-SD/01
29 (enrolled)
RCT
pegfilgrastim
filgrastim
40
(estimated
enrolled)
Open-label
interventio
nal