(Chest. 1999;116:1159-1162.)
© 1999
American College of Chest Physicians
Cyclophosphamide in the Treatment of Pulmonary Diseases*
Survey of Use, Training, and Practitioner Knowledge Base
Phillip J. Cozzi, MD and
Jesse B. Hall, MD, FCCP
*
From the Critical Care Section (Dr. Cozzi), Elmhurst Memorial Hospital, Elmhurst, IL; and the Section of Pulmonary and Critical Care Medicine (Dr. Hall), Department of Medicine, University of Chicago, Pritzker School of Medicine, Chicago, IL.
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Abstract
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Objective: To assess pulmonologists’ use, training in
the use, and knowledge base of the drug cyclophosphamide.
Design: Survey through questionnaire. Testing of knowledge
base before and after instructional conference.
Participants
and methods: Pulmonologists (94 attendings, 31 fellows), selected
randomly at the 1996 and 1997 annual meetings of The American Thoracic
Society, completed surveys of their use and training in the use of
cyclophosphamide. Thirty-five attending at the 1998 meeting completed a
test of knowledge base of the drug. Members of the pulmonary teaching
service at The University of Chicago Hospitals completed the test
before and after a case-based conference designed to educate
pulmonologists in the use of the drug.
Results:
Forty-three percent of the attending pulmonologists and 55% of the
fellows were currently using the drug in the management of their
patients; 77% of the attending pulmonologists had prescribed the drug
in the past. Nonmalignant diseases for which the drug was prescribed
included usual interstitial pneumonitis/desquamative interstitial
pneumonitis, vasculitis, collagen vascular disease, constrictive
bronchiolitis, sarcoid, and Goodpasture’s disease. Sixty-eight percent
of attending pulmonologists and 81% of fellows had no training in the
drug’s use. Of the attending pulmonologists who made use of the drug,
64% were prescribing and managing its use themselves. Of those who
prescribed and managed the drug’s use themselves, 65% had had no
training in its use. Of those fellows who prescribed and managed the
drug’s use themselves, 73% had had no training in the drug’s use. On
knowledge-based testing, the average correct score was 30 ± 10%.
With an educational conference, average pre- and post-test scores rose
from 40 ± 10% to 80 ± 10% (p < 0.001).
Conclusion: Cyclophosphamide had been used by the vast
majority of pulmonologists, either currently or in the past, for a wide
variety of lung diseases. Its use is commonly managed by physicians who
have no specific training relevant to this agent. Practitioner
knowledge base of the drug is poor, and case-based conferences in
fellowship may be an effective means of imparting information
concerning this drug.
Key Words: cyclophosphamide • survey • training • knowledge base
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Introduction
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Although
initially used to treat malignancies, cytotoxic drugs have been used in
the management of multiple other pulmonary diseases.
Cyclophosphamide is the most widely used agent in
this class, having complex modulatory effects on the immune
response.1
Pulmonary rheumatic diseases, vasculitides,
granulomatous states, and a variety of other conditions have been
treated with cyclophosphamide.2
Serious side effects,
including cytopenias, nausea, hepatotoxicity, pneumonitis, pulmonary
interstial fibrosis, hemorrhagic cystitis, gonadal toxicity,
teratogenicity, carcinoma of the bladder, and induction of other
neoplasms, have limited the drug’s use.3
Although
cyclophosphamide is considered integral to the management of Wegener’s
granulomatosis,4
uncertainty regarding efficacy has
further limited the drug’s use for other pulmonary and systemic
inflammatory disorders.
Little is known about the extent of use of cyclophosphamide by
pulmonologists nor the familiarity of these physicians with the
pharmacokinetics, immune effects, and toxicities of cyclophosphamide.
Considering the profile of serious side effects, training in the
management of the drug’s use is considered critical. We hypothesized
that cyclophosphamide is commonly used by pulmonologists, but that
training in the use of the drug is uncommon and that practitioner
knowledge base of the drug’s use is poor. Accordingly, we surveyed
pulmonologists’ use, training in the use, and knowledge base of
cyclophosphamide. One potential means of improving the
practitioner knowledge base of cyclophosphamide is the case-based
educational conference. We therefore tested the attendees’ knowledge
base before and after a case-based conference designed specifically to
educate in the use of cyclophosphamide.
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Materials and Methods
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At the 1996 and 1997 annual meetings of The American Thoracic
Society, we randomly surveyed 125 attending pulmonologists and fellows
regarding their use and training in the use of cyclophosphamide. The
survey instrument consisted of a single sheet of paper, one-sided, with
eight questions: name, country of practice, whether attending
pulmonologist or pulmonary fellow, number of patients they were
currently treating with cyclophosphamide, number of patients they had
treated with cyclophosphamide in the past, disease states for which
they had used cyclophosphamide, whether or not they had received any
training in the use of cyclophosphamide, and whether they managed the
drug’s use themselves or in conjunction with other specialists.
Thirty-five randomly selected attending pulmonologists at the 1998
meeting of the American Thoracic Society completed a 10-question test
of knowledge base of cyclophosphamide, including dosing, metabolism,
and screening for side effects. A case-presentation conference focusing
on the management of cyclophosphamide use was given to the University
of Chicago pulmonary teaching service. Pre- and postconference
knowledge base testing was performed, using the same 10-question test.
The participants then completed knowledge base testing again at the
1-year interval.
Data are reported as mean ± SD. Statistics were performed using
2 analyses. Statistical significance was
considered to exist when p < 0.05.
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Results
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The number of respondents from each country of origin represented
in the survey is shown in Table 1
. Pulmonologists from 14 different countries were surveyed, with 62%
being from the United States.
The respondents cited a variety of disease states for which they have
used cyclophosphamide (Table 2
). Sarcoidosis, idiopathic pulmonary fibrosis, and Wegener’s
granulomatosis were the three most commonly cited diseases. Only five
pulmonologists cited lung cancer as a disease for which they have used
cyclophosphamide.
Responses to questions regarding any current or past cyclophosphamide
use, and training in cyclophosphamide use, are shown in Table 3
. In the 1996 and 1997 American Thoracic Society surveys, 43% of
attending pulmonologists and 55% of fellows were currently prescribing
the drug. Seventy-seven percent of attending pulmonologists and 81% of
fellows had prescribed the drug in the past.
Among attending pulmonologists, the mean number of patients currently
being treated with cyclophosphamide was 3.1; among fellows, the
corresponding number was 1.9. Among attending pulmonologists, the mean
number of current or past patients treated with cyclophosphamide was
14.9; among fellows, the corresponding number was 3.7. Among only those
attending pulmonologists who had used cyclophosphamide, the mean number
of patients currently being treated with cyclophosphamide was 7.2;
among only those fellows who have used cyclophosphamide, the
corresponding number was 3.4.
Among all respondents who had used cyclophosphamide, 64% of the
attending pulmonologists and 60% of the fellows were prescribing and
managing the drug’s use themselves. Twenty-three physicians
(attendings and fellows) were prescribing in conjunction with a
rheumatologist. Eight physicians were prescribing in conjunction with
an oncologist. One attending was managing the drug’s use in
conjunction with a nephrologist. Only two fellows were prescribing and
managing the drug’s use in conjunction with attending pulmonologists.
Sixty-eight percent of the attending pulmonologists had no training in
the drug’s use; 81% of the fellows had no training in the drug’s
use. Among all attendings who prescribe and manage
cyclophosphamide use themselves, 65% had no training in the
drug’s use. Among all fellows who are prescribing and managing
cyclophosphamide use themselves, 73% had no training in the drug’s
use.
Among the thirty-five pulmonologists who completed the knowledge base
test at the 1998 American Thoracic Society meeting, the average correct
score was 30%. The third phase of the study, which tested members of
the pulmonary teaching service at the University of Chicago Hospitals,
demonstrated that significant learning was achieved after an
educational conference. Average pre- and postconference test scores
rose from 40 to 80% (p < 0.0001). Thirteen of the 15 participants
completed repeat testing at the 1-year interval with average scores of
60% (p < 0.001, compared to preconference testing), suggesting
sustained learning.
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Discussion
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Recognizing the limitation that a "survey" methodology relies
on physician recall, cyclophosphamide has been used by the vast
majority of practicing pulmonologists (77%) in one or more of their
patients. However, the average number of patients being
currently treated by attending pulmonologists is small.3
Concerns regarding the efficacy of the drug and the profile of serious
side effects have limited the drug’s use. As a second- or third-line
therapeutic, the drug is occasionally used when few alternatives exist.
Many of the disease states for which pulmonologists are currently using
cyclophosphamide are so-called "off-label" uses.
Despite the well-known risks of cyclophosphamide, training in the use
of the drug is relatively uncommon. Sixty-five percent of those who
prescribe and manage the drug’s use themselves had no training in the
use of the drug. One could argue that those physicians completed
fellowships before the availability of cyclophosphamide, yet few
pulmonary fellows today are being trained in the use of the drug. Low
scores on knowledge base testing of cyclophosphamide dosing,
metabolism, and screening for side effects suggest that pulmonologists
have a poor understanding of the drug’s use. Considering the serious
risks associated with cyclophosphamide use and the observation that
most pulmonologists have used or are currently using the drug, we
believe formal training in the use of cyclophosphamide should be
incorporated into all pulmonary fellowship programs.
Our data demonstrate that pulmonary practitioners and fellows use
cyclophosphamide, and that their training and knowledge base of the
drug is often meager or nonexistent. This begs the question as to how
to train them. We held a teaching conference with a case-presentation
format designed to be instructive in cyclophosphamide management. The
case-presentation format has been a traditional mode of medical
education and, in this circumstance, was very easily applied. Questions
for pre- and postconference testing were designed to assay knowledge
base of dosing, appropriate use, and avoidable toxicities. Significant
improvement in test scores suggest this may be one effective mode of
education in cyclophosphamide use, and the learning appears to be
sustained over a 1-year period. A potential limitation of the study was
the use of the same questions for the pre- and postconference testing,
and participants may have keyed into topics addressed in both the
pretest and the conference. Additionally, we note that even though lack
of training in cyclophosphamide use is common, we have no information
about whether this leads to inappropriate use or avoidable toxicities.
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Footnotes
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Correspondence to: Jesse B. Hall, MD, FCCP, Section of Pulmonary
and Critical Care, Department of Medicine, University of Chicago,
Pritzker School of Medicine, 5841 S. Maryland Ave, Chicago, IL 60637;
e-mail: jhall@medicine.bsd.uchicago.edu
Received for publication January 26, 1999.
Accepted for publication July 7, 1999.
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Abstract
Introduction
