ONCOLOGY.
No. 13
9
Selected Abstracts From ASCO and MASCC/ISOO 2004
Update on Neutropenia and the Use of Myeloid Growth Factors
By Jeffrey Crawford, MD |
November 3, 2004
There has been a remarkable explosion in medical
information over the past several years.
The rate of new discoveries and improved understanding
of the biology and treatment of
cancer is ever-increasing. The same is true in
the area of supportive cancer therapy.[1]
In the area of medical oncology we have been
confronting the problem of neutropenia related
to myelosuppressive chemotherapy treatment
for decades. Prior to the 1990s, our only approach
was to educate chemotherapy patients
about the risk of neutropenia, monitor their
blood counts periodically, and aggressively
manage neutropenia-related fever and infection.[
2,3] Because of the morbidity and mortality
associated with these neutropenic events,
patients who recovered adequately to undergo
further therapy generally received chemotherapy
dose reduction. This strategy was also used
as a primary approach at the initiation of
therapy for patients for whom the oncologist
was concerned that the risks and/or consequences
of development of neutropenia and
infection might outweigh the benefits of fulldose
treatment.
Treatment alternatives to change this paradigm
first occurred in 1991, with the clinical
approval of the colony-stimulating factors. The
use of colony-stimulating factors as primary
prophylaxis after myelosuppressive chemotherapy
allowed patients to reduce their risk of
neutropenic complications.[3] These agents
also provided an opportunity to try to maintain
full-dose chemotherapy in patients who had
experienced a neutropenic event on a prior
chemotherapy cycle.
However, over the past decade, the strategy of
secondary prophylaxis has been frequently
employed due to the limitations in our understanding
of individual patient risk. Primary
prophylaxis has also been limited by the American
Society of Clinical Oncology (ASCO)
guidelines. Most studies demonstrating benefit
have been performed in the setting of veryhigh-
risk chemotherapy regimens where the
expected incidence of febrile neutropenia was
in excess of 40%. Since most chemotherapy
regimens that are standard in clinical practice
have a substantially lower risk of febrile neutropenia,
and because our patient risk models
have not been well developed, the reactive
approach for use of colony-stimulating factors
has been the norm.
The results of this "watch and wait" approach
for the supportive management of neutropenia
are clearly seen in several of the abstracts from
the ASCO 40th Annual Meeting and the Multinational
Association for Supportive Care in
Cancer (MASCC)/International Society for
Oral Oncology (ISOO) 16th International Symposium,
both held earlier this year. The frequency
of neutropenia in clinical practice
remains alarmingly high, and the complications
in terms of inpatient hospitalization, morbidity,
mortality, and economic cost from the
University HealthSystem Consortium database
is staggering.
In 2002, a second-generation granulocyte
colony-stimulating factor (pegfilgrastim
[Neulasta]) was approved for use in the prevention
of chemotherapy-related neutropenia.
Clinical benefit from a single injection
postchemotherapy was equivalent to that of
daily dosing for more than 10 days of filgrastim(Drug information on filgrastim)
(Neupogen) in randomized trials.[4] In addition
to the advantages of improved technology
and better patient and provider convenience,
subsequent clinical trials have not only helped
us better understand the utility of pegfilgrastim,
but also helped us refine our use of colonystimulating
factors.
Included in the 2004 ASCO/MASCC abstracts
are important prospective studies that evaluate
the benefits of filgrastim or pegfilgrastim in
primary prevention of neutropenic complications
in patient populations receiving chemotherapy
where the risk of febrile neutropenia is
substantially less than 40%. As the reader will
see in the pages ahead, risk reduction may be
even greater in these lower-risk myelosuppressive
settings.
In addition to improving our understanding of
the epidemiology of neutropenia and its consequences
and the ability to redefine our threshold
of primary prophylaxis with colony-
stimulating factors, the 2004 ASCO and
MASCC/ISOO abstracts also provide a wealth
of information in the disease-specific areas of
breast cancer, lung cancer, lymphoma, and
hematologic malignancies. I invite the reader
to review all of the sections carefully to better
refine your understanding of the prevention
and management of neutropenia in cancer chemotherapy
patients within your own practice.
In 2005 the ASCO guidelines will be updated,
and we will see for the first time the National
Comprehensive Cancer Network guidelines on
the use of colony-stimulating factors. The impact
of the abstracts included in this supplement
to ONCOLOGY will be substantial. As a
result, we will hopefully move closer to reducing
the morbidity of chemotherapy while improving
our ability to deliver full-dose therapy
when appropriate to enhance overall patient
outcomes. For this to happen, the oncology
community must work closely together not only
to conduct the appropriate research, but to
educate one another about the results. I am
hopeful that the abstracts and commentary in
the pages ahead will help us all in that process.
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Cancer Types
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Supportive Care
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More Topics
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