2006 Update of ASCO Practice Guideline Recommendations

for the Use of White Blood Cell Growth Factors:

Guideline Summary
Context
ASCO convened an Update Committee composed of the
original Expert Panel and select ad hoc members to present
the 2006 evidence-based clinical practice guideline update
(J Clin Oncol 24:3187-3205, 2006) for the use of
hematopoietic colony-stimulating factors (CSF).
Updated 2006 Recommendations
See Table 1 for a summary of the updated 2006
recommendations and specic considerations. Table A1 lists
the incidence of toxicities associated with selected
chemotherapy regimens.
1. Primary Prophylactic CSF Administration
(rst and subsequent-cycle use)
Clinical trial data support the use of CSF when the risk of
febrile neutropenia (FN) is in the range of 20% or higher.
This recommendation represents a departure from the 2000
update, which recommended the use of CSF when the risk of
FN was 40% or higher. Most commonly used regimens have
an FN risk of less than 20%. Oncologists should consider the
optimal chemotherapy regimen, individual patient risk factors
and treatment intention when deciding whether to use
prophylactic CSF. The use of regimens that do not require
CSF because of equal efcacy and lower risk of FN remains
standard medical practice.
2. Secondary Prophylactic CSF Administration
Secondary prophylaxis with CSF is recommended for a select
group of patients. Oncologists should be mindful of previous
neutropenic complications, prior CSF administration, and
appropriateness of dose reduction. No denitive conclusions
can be drawn regarding the benets of secondary prophylaxis
on survival, quality of life, or cost.
3. Therapeutic Use of CSF
Therapeutic intervention with CSF can help reduce the
incidence of infectious episodes and infection-related
morbidity and mortality. However, therapeutic CSF use
should be reserved for patients with fever and neutropenia
and those at high risk for infection-associated complications
or poor clinical outcomes. This intervention should not be
routinely used in afebrile patients or FN patients receiving
antibiotic therapy. Clinical prediction models have been
developed to help prospectively identify patients with cancer
who are at higher risk of complications as a result of fever and
neutropenia; a risk model for mortality in hospitalized
patients has also been reported recently (Table 2).
4. Use of CSF to Increase Chemotherapy Dose
Intensity and Dose Density
Data on using CSF to increase dose-intensity or -density
chemotherapy regimens are limited. Evidence has shown that
the use of CSF allows for a moderate increase in dose-dense
(but not dose-intense) regimens in certain settings (e.g., node-
positive breast cancer; and possibly non-Hodgkins
lymphoma pending conrmation of results of individual
trials). This treatment approach should only be used within
the constructs of a clinical trial or if supported by
appropriate evidence.
5. Use of CSF As Adjuncts to Progenitor-
Cell Transplantation
Major complications of high-dose chemotherapy supported
by autologous bone marrow transplantation or peripheral-
blood progenitor cell (PBPC) transplantation include disease
recurrence, infection, delayed or incomplete engraftment, and
organ damage from the ablative regimen. The use of CSF to
mobilize PBPC and to shorten the period of neutropenia after
cytoreduction and PBPC transplantation is well established.
6. Use of CSF in Patients With Acute Leukemia and
Myelodysplastic Syndromes
Considerations and available evidence vary for acute myeloid
leukemia (AML), myelodysplastic syndrome (MDS), acute
lymphocytic leukemia (ALL), and acute leukemia in relapse.
Several studies have shown that CSF administration can
produce modest decreases in the duration of neutropenia
when begun shortly after completion of the initial induction
chemotherapy for patients with AML. Studies on CSF
priming of leukemia cells in patients with AML produced
results showing no effect on complete response rates or overall
survival. Additional studies on AML patients (those in
remission) showed a seemingly profound shortened duration
of neutropenia after consolidation chemotherapy. These
studies produced no effect on complete response duration or
overall patient survival. Though CSF use can increase the
absolute neutrophil count in neutropenic patients with MDS,
data supporting the routine, long-term, continuous use of
CSF for this population are lacking. Using CSF for patients
with ALL (after initial chemotherapy induction or
postremission course) may shorten the duration of
neutropenia by 1 week. However, CSF use in patients with
relapsed or refractory acute leukemia may provide only a few
days of shortened neutropenia.
Whats New in JCO
196 JOURNAL OF ONCOLOGY PRACTI CE VOL. 2, I SSUE 4 Copyright 2006 by American Society of Clinical Oncology.
All rights reserved.
D
o
w
n
l
o
a
d
e
d

f
r
o
m

j
o
p
.
a
s
c
o
p
u
b
s
.
o
r
g

o
n

A
p
r
i
l

1
4
,

2
0
1
4
.

F
o
r

p
e
r
s
o
n
a
l

u
s
e

o
n
l
y
.

N
o

o
t
h
e
r

u
s
e
s

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n
.
C
o
p
y
r
i
g
h
t

2
0
0
6

A
m
e
r
i
c
a
n

S
o
c
i
e
t
y

o
f

C
l
i
n
i
c
a
l

O
n
c
o
l
o
g
y
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.
Table 1. Summary of 2006 Recommendations for the Use of CSF
Setting/Indication Recommendation
Primary prophylaxis Primary prophylaxis is recommended for the prevention of FN in patients who have a high risk of FN based on
age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. For dose-dense
regimens, CSF is required and recommended. Clinical trial data support the use of CSF when the risk of FN is in
the range of 20% or higher.
Primary prophylaxis: Special
circumstances
Certain clinical factors predispose to increased complications from prolonged neutropenia, including: patient age
65 years; poor performance status; previous episodes of FN; extensive prior treatment including large radiation
ports; administration of combined chemoradiotherapy; bone marrow involvement by tumor-producing
cytopenias; poor nutritional status; the presence of open wounds or active infections; more advanced cancer, as
well as other serious comorbidities. In such situations, primary prophylaxis with CSF is often appropriate, even
with regimens with FN rates of 20%.
Secondary prophylaxis Secondary prophylaxis with CSF is recommended for patients who experienced a neutropenic complication from
a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which a reduced dose may
compromise disease-free or overall survival or treatment outcome. In many clinical situations, dose reduction or
delay may be a reasonable alternative.
Therapeutic use: Afebrile
neutropenia
CSF should not be routinely used for patients with neutropenia who are afebrile.
Therapeutic use: Febrile
neutropenia
CSF should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and
neutropenia. However, CSF should be considered in patients with fever and neutropenia who are at high-risk for
infection-associated complications, or who have prognostic factors that are predictive of poor clinical outcomes.
High-risk features include expected prolonged ( 10 days) and profound ( 0.1 109/L) neutropenia, age 65
years, uncontrolled primary disease, pneumonia, hypotension and multi-organ dysfunction (sepsis syndrome),
invasive fungal infection, or being hospitalized at the time of the development of fever.
Dose intensity/density of
chemotherapy
Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by
convincing efcacy data.
Adjuncts to progenitor-cell
transplantation
Administration of CSF to mobilize PBPC often in conjunction with chemotherapy, and their administration after
autologous, but not allogeneic, PBPC transplantation is the current standard of care.
AML: Initial or repeat
induction chemotherapy
CSF use following initial induction therapy is reasonable, though there has been no favorable impact on remission
rate, remission duration, or survival. Patients 55 years of age may be most likely to benet from CSF use.
AML: CSF for priming
effects
Use of CSF for priming effects is not recommended.
AML: Consolidation
chemotherapy
CSF use can be recommended after the completion of consolidation chemotherapy because of the potential to
decrease the incidence of infection and eliminate the likelihood of hospitalization in some patients receiving
intensive postremission chemotherapy. There seems to be more profound shortening of the duration of
neutropenia after consolidation chemotherapy for patients with AML in remission than for patients receiving initial
induction therapy. As yet there is no information about the effect of longer-acting pegylated CSFs in patients with
myeloid leukemias, and they should not be used in such patients outside of clinical trials.
MDS Intermittent administration of CSF may be considered in a subset of patients with severe neutropenia and
recurrent infection.
ALL CSF administration is recommended after the completion of the initial rst few days of chemotherapy of the initial
induction or rst postremission course, thus shortening the duration of neutropenia of 1,000/mm
3
by
approximately 1 week.
Acute leukemia in relapse CSF should be used judiciously, or not at all, in patients with refractory or relapsed myeloid leukemia since the
expected benet is only a few days of shortened neutropenia.
Radiotherapy
chemotherapy
CSF should be avoided in patients receiving concomitant chemotherapy and radiation therapy, particularly
involving the mediastinum. In the absence of chemotherapy, therapeutic use of CSF may be considered in
patients receiving radiation therapy alone if prolonged delays secondary to neutropenia are expected.
Older patients Prophylactic CSF for patients aged 65 years with lymphoma treated with curative chemotherapy (CHOP or
more aggressive regimens) should be given to reduce the incidence of FN and infections.
Pediatric patients As in adults, the use of G-CSF is reasonable for the primary prophylaxis of pediatric patients with a likelihood of
FN. Similarly, the use of G-CSF for secondary prophylaxis or for therapy should be limited to high-risk patients.
However, the potential risk for secondary myeloid leukemia or myelodysplastic syndrome associated with G-CSF
represents a concern in children with ALL whose prognosis is otherwise excellent. For these reasons, the specic
use of G-CSF in children with ALL should be considered carefully.
Continued on next page
JULY 2006 www. j opasco. org 197 Copyright 2006 by American Society of Clinical Oncology.
All rights reserved.
D
o
w
n
l
o
a
d
e
d

f
r
o
m

j
o
p
.
a
s
c
o
p
u
b
s
.
o
r
g

o
n

A
p
r
i
l

1
4
,

2
0
1
4
.

F
o
r

p
e
r
s
o
n
a
l

u
s
e

o
n
l
y
.

N
o

o
t
h
e
r

u
s
e
s

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n
.
C
o
p
y
r
i
g
h
t

2
0
0
6

A
m
e
r
i
c
a
n

S
o
c
i
e
t
y

o
f

C
l
i
n
i
c
a
l

O
n
c
o
l
o
g
y
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.
7. Use of CSF in Patients Receiving Radiotherapy
With or Without Concurrent Chemotherapy
Though concurrent chemotherapy with radiation therapy is
important in certain treatment settings, oncologists should
avoid CSF administration for these patients. However, in the
absence of chemotherapy, and if prolonged delays secondary
to neutropenia are expected, patients receiving radiation
therapy alone may benet from the therapeutic use of CSF.
8. Use of CSF in Older Patients: New Topic
Aging is one of the conditions for which prophylactic use of
growth factors may be indicated irrespective of the threshold
risk of neutropenia. However, aside from data available in
patients with lymphoma, there is insufcient evidence to
support the use of prophylactic CSF in patients, based solely
on age. Oncologists should consider additional patient risk
factors when deciding whether to administer CSF to
elderly patients.
9. Use of CSF in the Pediatric Population
The use of CSF in pediatric patients will almost always be
guided by clinical protocols. Several multicenter randomized
clinical trials have evaluated prophylactic CSF in children,
particularly those with acute leukemia. Based on this research,
oncologists should consider cautiously the use of CSF in
children with ALL. When determining whether CSF
administration would prophylactically or therapeutically
benet a pediatric patient, the oncologist should consider the
patients likelihood of developing FN and incidence of other
risk factors.
10. CSF Initiation, Duration, Dosing,
and Administration
Filgrastim (G-CSF), peglgrastim (pegylated G-CSF), and
sargramostim (GM-CSF) are the growth factors currently in
use. The administration protocol for each agent varies
according to setting (Table 3).
Table 1. Summary of 2006 Recommendations for the Use of CSF (continued)
Setting/Indication Recommendation
Comparative clinical activity
of G-CSF and GM-CSF
No guideline recommendation can be made regarding the equivalency of the two colony-stimulating agents.
Further trials are recommended to study the comparative clinical activity, toxicity, and cost-effectiveness of G-
CSF and GM-CSF.
Treatment for radiation
injury
Current recommendations for the management of patients exposed to lethal doses of total-body radiotherapy,
but not doses high enough to lead to certain death due to injury to other organs, includes the prompt
administration of CSF or pegylated G-CSF.
Abbreviations: CSF, colony-stimulating factors; FN, febrile neutropenia; PBPC, peripheral-blood progenitor cell; AML, acute myeloid leukemia;
MDS, myelodysplastic syndrome; ALL, acute lymphocytic leukemia; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; G-CSF,
lgrastim; GM-CSF, sargramostim; pegylated G-CSF, peglgrastim.
Table 2. Clinical Prediction and Risk Models
Clinical Prediction Model for Prospectively
Identifying Cancer Patients at Higher Risk of
Complications due to Fever and Neutropenia:
Reported Risk Factors for Serious Medical
Complications in Patients With Established FN
Risk Model for Mortality in Hospitalized Patients: Independent Risk Factors
for Inpatient Mortality in Hospitalized Patients With FN
Development of FN as inpatient Comorbidities: CHF, PE, lung, renal, liver, and cerebrovascular disease
Hypotension Infectious complications: hypotension, pneumonia, bacteremia, fungal infection
Sepsis Cancer type (leukemia, lung cancer)
Cardiovascular disease Age 65 years
Pulmonary disease
Leukemia or lymphoma diagnosis
Age 65 years
Prior fungal infection
Visceral organ involvement
Organ dysfunction
Uncontrolled malignancy
Severity and duration of neutropenia
Abbreviations: FN, febrile neutropenia; CHF, congestive heart failure; PE, pulmonary embolism.
198 JOURNAL OF ONCOLOGY PRACTI CE VOL. 2, I SSUE 4 Copyright 2006 by American Society of Clinical Oncology.
All rights reserved.
D
o
w
n
l
o
a
d
e
d

f
r
o
m

j
o
p
.
a
s
c
o
p
u
b
s
.
o
r
g

o
n

A
p
r
i
l

1
4
,

2
0
1
4
.

F
o
r

p
e
r
s
o
n
a
l

u
s
e

o
n
l
y
.

N
o

o
t
h
e
r

u
s
e
s

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n
.
C
o
p
y
r
i
g
h
t

2
0
0
6

A
m
e
r
i
c
a
n

S
o
c
i
e
t
y

o
f

C
l
i
n
i
c
a
l

O
n
c
o
l
o
g
y
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.
11. Special Comments on Comparative Clinical
Activity of G-CSF and GM-CSF
No guideline recommendation can be made regarding the
equivalency of the two colony-stimulating agents. As in 2000,
further trials are recommended to study the comparative
clinical activity, toxicity, and cost-effectiveness of G-CSF
and GM-CSF.
12. Special Comments on Growth Factors As a
Treatment for Radiation Injury: New Topic
Current recommendations for the management of patients
exposed to lethal doses of total-body radiotherapy, but not
doses high enough to lead to certain death due to injury to
other organs, includes the prompt administration of CSF or
pegylated G-CSF.
13. Impact of CSF on Quality of Life and Health
Care Costs
Growth factors should be used when indicated for clinical
reasons, not economic ones. When available, alternative
regimens offering equivalent efcacy but not requiring CSF
support should be utilized. Further research into CSF cost
implications and impact on quality of life is warranted.
Discussion
The 2006 Update Committee was guided by the 1996 ASCO
outcomes criteria that justify the use of a drug or technology
based on improvements in survival, quality of life, toxicity
reduction, and cost-effectiveness. The Committee agreed
unanimously that reduction in FN was an important clinical
outcome that justied use of CSF, regardless of impact on
other factors, when the risk of FN was about 20% and no
other equally effective regimen that did not require CSF
was available.
Methodology
The 2006 Update Committee performed a complete
literature review and analysis of data published from 1999
through September 2005. Whenever possible, the Committee
focused on randomized controlled trials and systematic
reviews and meta-analyses of published trials.
Additional Resources
The 2006 Update is available in the July 1, 2006, print
edition of JCO and also at www.jco.org (J Clin Oncol
24:3187-3205, 2006). In addition to the full text of the
guideline recommendations, available online at http://
www.asco.org/guidelines/wbcgf, further resources from
ASCO include a patient guide and PowerPoint slide set.
A CSF ow sheet and orders form is available online at
www.jopasco.org.
Table 3. Recommendations for CSF Initiation, Duration, Dosing, and Administration
Growth Factor Setting Initiation Duration Dose
G-CSF (lgrastim) Myelotoxic chemotherapy 24-72 hours after
administration of
chemotherapy
Continue until ANC at least
2-3 10
9
/L
Adults: 5 g/kg/d
subcutaneous
High-dose therapy and
autologous stem-cell
rescue
24-120 hours after
administration of high-
dose therapy
Continue until ANC at least
2-3 10
9
/L
Adults: 5 g/kg/d
subcutaneous
PBPC mobilization Start at least 4 days before
rst leukapheresis
Continue until last
leukapheresis
Adults: 10 g/kh/d
subcutaneous
Pegylated G-CSF
(peglgrastim)*
Myelotoxic chemotherapy 24 hours after completion
of chemotherapy
Once in each
chemotherapy cycle
6 mg
GM-CSF (sargramostim) Bone marrow
transplantation or AML
Day of bone marrow
infusion and not less than
24 hours from the last
chemotherapy and 12
hours from most recent
radiotherapy
Continue until ANC 1.5
10
9
/L for 3 consecutive
days
Adults: 250 g/m
2
/d for all
clinical settings other than
PBPC mobilization
NOTE. The long-term effects of long acting growth factors are unknown, and the Update Committee expressed concern about potential
leukocytosis, late neutropenia after discontinuation of pegylated G-CSF, and the need for long-term safety data.
Abbreviations: G-CSF, lgrastim; ANC, absolute neutrophil count; PBPC, peripheral-blood progenitor cell; pegylated G-CSF, peglgrastim; GM-
CSF, sargramostim.
* Peglgrastim is not currently indicated for stem-cell mobilization. The safety and efcacy of pegylated G-CSF has not yet been established in the
setting of dose-dense chemotherapy.
The 6-mg formulation should not be used in infants, children, or small adolescents weighing 45 kg.
Because GM-CSF has been licensed specically for use after autologous or allogeneic BMT and for AML, the manufacturers instructions for
administration are limited to those clinical settings.
The drug should be discontinued early or the dose be reduced by 50% if the ANC increases to 20 10
9
/L.
JULY 2006 www. j opasco. org 199 Copyright 2006 by American Society of Clinical Oncology.
All rights reserved.
D
o
w
n
l
o
a
d
e
d

f
r
o
m

j
o
p
.
a
s
c
o
p
u
b
s
.
o
r
g

o
n

A
p
r
i
l

1
4
,

2
0
1
4
.

F
o
r

p
e
r
s
o
n
a
l

u
s
e

o
n
l
y
.

N
o

o
t
h
e
r

u
s
e
s

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n
.
C
o
p
y
r
i
g
h
t

2
0
0
6

A
m
e
r
i
c
a
n

S
o
c
i
e
t
y

o
f

C
l
i
n
i
c
a
l

O
n
c
o
l
o
g
y
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.
The ASCO 2006 Update of Recommendations for the Use of
White Blood Cell Growth Factors was developed and written by
Thomas J. Smith (Chair), James Khatcheressian, Gary H.
Lyman, Howard Ozer, James O. Armitage, Lodovico
Balducci, Charles L. Bennett, Scott B. Cantor,
Jeffrey Crawford, Scott J. Cross, George Demetri,
Christopher E. Desch, Philip A. Pizzo, Charles A. Schiffer,
Lee Schwartzberg, Mark R. Somereld, George Somlo,
James C. Wade, James L. Wade, Rodger J. Winn,
Antoinette J. Wozniak, and Antonio C. Wolff.
Assess and Improve Care in Your Medical Oncology Practice
The goal of ASCOs Quality Oncology Practice Initiative (QOPI) is to promote excellence in cancer care by helping
medical oncologists create a culture of self-examination and improvement.
QOPI practices benet from knowledge of practice strengths and weaknesses and access to tools and strategies to
improve care. By participating in QOPI, physicians receive practice-specic data, aggregate data from their peers
for comparison, and access to resources for implementing best practices. All practice-specic data are released only to
that practice, and are kept strictly condential.
Join the oncologist-led initiative for assessing and improving care
in medical oncology practice.
Visit www.asco.org/QOPI. AMERICAN SOCIETY OF CLINICAL ONCOLOGY
It is important to realize that many management questions have not been comprehensively addressed in randomized trials and
guidelines cannot always account for individual variation among patients. A guideline is not intended to supplant physician
judgment with respect to particular patients or special clinical situations and cannot be considered inclusive of all proper methods of
care or exclusive of other treatments reasonably directed at obtaining the same results.
Accordingly, ASCO considers adherence to this guideline to be voluntary, with the ultimate determination regarding its application
to be made by the physician in light of each patients individual circumstances. In addition, the guideline describes administration
of therapies in clinical practice; it cannot be assumed to apply to interventions performed in the context of clinical trials, given that
clinical studies are designed to test innovative and novel therapies in a disease and setting for which better therapy is needed.
Because guideline development involves a review and synthesis of the latest literature, a practice guideline also serves to identify
important questions for further research and those settings in which investigational therapy should be considered.
200 JOURNAL OF ONCOLOGY PRACTI CE VOL. 2, I SSUE 4 Copyright 2006 by American Society of Clinical Oncology.
All rights reserved.
D
o
w
n
l
o
a
d
e
d

f
r
o
m

j
o
p
.
a
s
c
o
p
u
b
s
.
o
r
g

o
n

A
p
r
i
l

1
4
,

2
0
1
4
.

F
o
r

p
e
r
s
o
n
a
l

u
s
e

o
n
l
y
.

N
o

o
t
h
e
r

u
s
e
s

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n
.
C
o
p
y
r
i
g
h
t

2
0
0
6

A
m
e
r
i
c
a
n

S
o
c
i
e
t
y

o
f

C
l
i
n
i
c
a
l

O
n
c
o
l
o
g
y
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.
Table A1. Incidence of Hematologic and Infectious Toxicities Associated With Selected Chemotherapy Regimens
Cancer
Histology
Stage and Prior
Therapy Regimen
No. of
Patien
ts
Grade 4
Leukopenia
(%)*
Grade 4
Neutropenia
(%)
Febrile
Neutropenia (%)
Grade 2
Fever
(%)
Grade 3
Infection
(%)
Infectious
Death (%)
Adult AML Newly diagnosed Ara-C/DNR 163 93 37 (no
infection)
64 12
AIDS-related
Kaposi's sarcoma
Advanced/1st and 2nd
line
Lipo Dox [+G(M)-CSF]
VP16 (oral)
Paclitaxel
133
36
56
36 (3+4)

6
19.4
35

1
8

AIDS-related
NHL
Intermediate- and high-
grade, untreated
CHOP (Modified)
CHOP + G-CSF
40
25

25 (3+4)
13 (3+4)
2.5
0

10

Bladder Advanced, no prior

systemic therapy
Prior adjuvant allowed
GC
MVAC
CBDCA/Pac G-CSF
203
202
33

29.9
65.2
21
2
14
21
0
3.1

2.5
15.1
1 patient sepsis
1
2.5
0
Breast Adjuvant
Adjuvant (dose dense)
Metastatic (1st line)
Metastatic (2nd line)
CA (60 mg/m
2
)
CAT (all dose levels)
CEF
TAC
ATC
ATC + G-CSF
ACT
ACT + G-CSF
A (75)
Doc (100)
AC
AT
TAC
Cap Doc
Doc
1060
1590
351
109
484
493
501
495
165
161
215
214
54
255
256

49.9

11
6

62
16
89.7

24
3
43
9
77.8
78.6
88 (3+4)
97 (3+4)
100 (3+4)
11
12
10 (hospitalized)
3
8.5
23.8
3
2
6
2
12.3
5.7
10
33
34
16
21

17
11

3
4
5
3
4.3
2.5
2
8
2

0
0
0

0
0
0
0
1 death
1 death
0.5
0
0
< 1
0
Colorectal Adjuvant
Advanced
Advanced (one prior
chemo allowed)
5-FU/LV/L
5-FU/LV
IFL
FL
I
FOLFOX4
FOLFIRI
CPT-11 (350 mg/m
2
Q3
wk)
449
116
189
226
226
152
145
213
2
15 (high LV)
22 (low LV)

20.4 (3+4)
36 (3+4)

24
42.5
12.1
17
28.8 (3+4)
48 (3+4)

7.1
14.6
5.8
6
9.3
14

1.8
0
2.2

1.9
<1
< 1
1.7
< 1
1.4
< 1
0
< 1
3 deaths
Gastric
Advanced ECF (infusion) 289 13 32 1 6 <1
Germ cell Advanced
Relapsed
BEP
VIP
VeIP
141
145
135

34 (all heme 60
toxicities)

71

2
2.8
2.1 (all
deaths)
Head/neck Recurrent; metastatic
Induction
FU/CBDCA
CBDCA/Pac
Cis/Doc
Cis/Doc/FU
86
41
36
43
2.3
4.9

1.2
9.8
71
95 (3+4)

6
19

11
2
1.2
2.4
0
0
Lung Extensive SCLC
No prior treatment
Recurrent
Advanced NSCLC
No Prior Treatment
Recurrent (2
nd
line)
Cis/VP-16
CAV
CBDCA/VP-16
Cis/CPT-11
Topo
CAV
Cis/VNR
Cis/Pac (24 hr)
Cis/Gem
Cis/Doc
CBDCA/Pac
CBDCA/Doc
Doc (75 mg/m
2
)
Pemetrexed
159
156
74
77
107
104
206
288
288
289
290
406
276
265
14
28
5
4
31.7
43.6

49.5 (3+4)
40.2 (3+4)
5.3 (3+4)
38
52

25.3
70.2
71.7
59
57
39
48
43
74.4 (3+4)

28
26
10
16
4
11
4
3.7
12.7
1.9

1.3

8
16

5.3
4.7
4.8

10
7
9
6
11
3.3
0
6 (all toxic
deaths)
4 (all toxic
deaths)
0
2.6
3.7
2.9
1
2
1
2
1

Lymphoma Relapsed HD; prior

RT only
Intermediate- and high-
grade
NHL; no prior treatment
Relapse NHL
MOPP
ABVD
CHOP
CHOP-R
VAPEC-B
ESHAP
DHAP
123
115
216
33
39
122
90

25
1.2

22
3
22
58
72
500/_L median
53

18
44
30
48
3 (no infection)
5 (no infection)

13
2
5 ( grade 4)
6
5 patient

31
1
0
1
0
2 deaths
4.1
11
Multiple myeloma Untreated
Recurrent/refractory
VAD Inf
VAD Inf
169
52

65.4

32.7
1.2
7.7
Ovary Resected, minimal
residual
Salvage
Cis/Pac (24 hours)
CBDCA/Pac
Topo
400
392
139
12
6
30.1
78
72
82.4
Few instances

18

0
Sarcoma Advanced, untreated AD
MAID
A
AI
CYVADIC
186
188
263
258
142
32
86
13
32
15
38
79

5.3 (all study

arms)

11 (all study arms)

0
3.5

Special populations
(elderly)
NHL, untreated
Breast, adjuvant
CHOP
CHOP-R
CMF
197
202
76

4 (grade 3)

5 (3+4)
2

20
12

16 patients
(both arms)
0
* Grade 4 leukopenia: WBC count < 1.0 10
9
/L; grade 4 neutropenia: ANC < 0.5 10
9
/L.
Most patients received antiretroviral therapy and data do not include opportunistic infections.
Common toxicity criteria fever grade 2; 38.1C ( 100.5F).
Infection grade 3: systemic infection requiring hospitalization.
JULY 2006 www. j opasco. org 201 Copyright 2006 by American Society of Clinical Oncology.
All rights reserved.
D
o
w
n
l
o
a
d
e
d

f
r
o
m

j
o
p
.
a
s
c
o
p
u
b
s
.
o
r
g

o
n

A
p
r
i
l

1
4
,

2
0
1
4
.

F
o
r

p
e
r
s
o
n
a
l

u
s
e

o
n
l
y
.

N
o

o
t
h
e
r

u
s
e
s

w
i
t
h
o
u
t

p
e
r
m
i
s
s
i
o
n
.
C
o
p
y
r
i
g
h
t

2
0
0
6

A
m
e
r
i
c
a
n

S
o
c
i
e
t
y

o
f

C
l
i
n
i
c
a
l

O
n
c
o
l
o
g
y
.

A
l
l

r
i
g
h
t
s

r
e
s
e
r
v
e
d
.