Origird Article

Antipyretic Effect of Naproxen and

Corticosteroids on Neoplastic Fever
Jae C. Chang
Department of Medicine, Wright State University School of Medicine, und Hematology
&3 Oncology Section, Good Samaritan Hospital & Health Center, Dayton, Ohio

Abstract
Thirty-nine patients with advanced cancer and neoplastic feuer were retrospectively
analyzed to compare the antipyretic activity of naproxen and corticosteroids. The
diagnosis of neoplastic jker was well-otablished at the time of the administration of
naproxen or corticosteroid,s. All patients received nuproxen, and this treatment induced
complete lysis of fever in 36 patients (9OYo). Twelve of these patients also received
corz’icosteroids at another time; all had previously responded with complete lysis of fever
to naproxen. Corticosteroids induced complete lysis in six OJ these patients (50%),
partial lysis in two and no lysis in four. This observation suggests that naproxen is a
more effective antipyretic agent in the management of neoplastic fever than
corticosteroids. J Pain Symptom Manag 1988;3:141-4.

Key Words
Antipyretics, neoplastic jker, nuproxen, corticosteroids

Roth naproxen, a nonsteroidal anti-inflam- Table 1

Criteria for Neoplastic Fever
matory drug, and various corticosteroids have
been demonstrated to have antipyretic activity 1. Temperature elevation at least once above IO 1
in certain settings. Corticosteroids have been degrees Fahrenheit
shown to suppress fever caused by infections, 2. Duration of fever over one week above 10 1
allergic reaction, collagen vascular diseases, and degrees Fahrenheit
3. Lack of evidence of infection on physical
neoplasms’~‘]. Naproxen has been proven to examination
possess a selective antipyretic activity against 4. Negative results of adequate blood and urine
neoplastic fever’~“‘. This retrospective study was cultures
performed to compare the antipyretic activity 5. Absence of an infiltrate on chest
of these agents in patients with neoplastic fe- roentgenographl
6. Normal findings in spinal fluid in patients who
ver. underwent spinal puncture
7. Lack of evidence of non-infectious fever such
as drug reaction, transfusion reaction, etc.
Patients and Methods 8. Lack of infection on continuous evaluation
during hospitalization
The medical records of thirty-nine patients
9. Lack of response to adequate empirical
with proven diagnosis of neoplastic fever antibiotic therapy
treated at the Good Samaritan Hospital and
Health Center, Dayton, Ohio from November,
1982 to June, 1986, were reviewed. All patients
Address r-eprint requests to: Jae C. Chang, M.D., Good had advanced cancer. The diagnosis of neo-
Samaritan Hospital & Health Center, Dayton, Ohio
4Fi406 plastic fever was well-established on the basis
Accepted ,for publzcatzon: May 9, 1988 of the criteria (Table 1) previously described7,x.
 142 Chang Journal of Pain and Symptom Managemeqt

All patients had adequate trials of antipyretic
therapy using acetyl salycylic acid or acetami-
nophen, but no significant change in fever pat-
tern was observed. All patients were treated
intermittently with naproxen for neoplastic fe-
ver. To assess the antipyretic activity of corti-
costeroids, those patients who received a dose
of corticosteroid equivalent to 100 mg of hy-
drocortisone or more per day while not re-
ceiving naproxen were identified. Each of these
patients received the corticosteroid for 2 or
more days during the febrile period (at least
periodic temperature spikes above 10 1 degrees
Fahrenheit). Patients with fever due to side ef-
fects of chemotherapy and infection were ex-
cluded.
In all patients, naproxen treatment was ini-
tiated when the patient had fever above 101
degrees Fahrenheit at a dosage of 250 mg twice
a day. If defervescence was prompt and com-
plete, naproxen was continued for more than
3 days, until improvement of flushing, sweat-
ing, chills and fatigue was noted. If lysis of fever
was absent or partial, the naproxen dosage was
increased to 375 mg twice daily. If lysis of fever
did not occur with this dosage within 3 days,
naproxen was discontinued.
Corticosteroids were not administered for
antipyretic effect, but for such reasons as
thrombocytopenia, or as an element of chem-
otherapy. The specific corticosteroids and their
dosages were identified. The antipyretic activity
of both naproxen and corticosteroids was de-
termined according to the definitions previ-
ously described (Table 2)“.
Results
All thirty-nine patients with neoplastic fever
were treated with naproxen. Thirty-six patients
had complete response and three patients par-
tial response. Of the thirty-nine patients, twelve
also received an adequate dose and duration
of a corticosteroid during a febrile period not
otherwise treated with naproxen. Clinical data
on these patients and the antipyretic effect of
naproxen and corticosteroids on the neoplastic
fever are shown in Table 3. All twelve patients
had complete response with lysis of fever to
naproxen 250 mg twice per day except for pa-
tients 1 and 12, both of whom defervesced at
a higher dose, 375 mg twice daily. Defervesc-
ence always occurred within 12 hours after ini-
tiation of naproxen, and an afebrile state was
sustained as long as the patient was maintained
on naproxen.
The generic names and dosages of pre-
scribed corticosteroids are also shown in Table
3. Five patients received the drugs as a part of
chemotherapy regimen, two for thrombocy-
topenia, five as a supportive measure in a se-
vere toxic state. Seven patients received cor-
ticosteroids for a short term prior to naproxen
administration, and five patients had the drugs
after trial of naproxen and during relapse of
fever. Complete response of neoplastic fever
occurred to corticosteroids in six patients, par-
tial response in two patients, and no response
in four patients.

Table 2
Criteria for Responses of Neoplastic Fever to
Naproxen Treatment

Complete Complete lysis of fever to less than 99

Response: degrees Fahrenheit within 12 hours
after the initiation of the drug and
sustained normal temperature below
I I III I I I II 11 1 99 degrees Fahrenheit for at least 3
26 27 26 29 30 31 1 2 3 4 5 6 successive days while receiving the
May 1983 June 1983 drug
Fig 1. Febrile course of Patient 3 with neoplastic fever due Partial Reduction of fever following the drug
to stage IV-B Hodgkin’s disease. A prompt and complete Response: within 12 hours after administration
lysis of fever occurred in response to naproxen treatment. of the drug but persistent fever up to
However, fever recurred to the pretreatment level follow- 100 degrees Fahrenheitwhile degrees
ing the withdrawal of naproxen, and a high dose of pred- Fahrenheit while receiving the drug
nisone had no effect on the neoplastic fever.
Vol. 3 No. 3 Summer 1988 Cortzcosteroids on Neoplastic Fever 143

Table 3
Clinical Information on Patients with Neoplastic Fever

Response of Neoplastic Fever

Fever Highest to
Patient Age 8c Duration Temp. Steroids
Number Sex Diagnosis (weeks) (F) & Dosage Naproxcn Steroids

I 62/M Multiple myeloma 44+ 104.0 Hydrocortisone Complete* Complete

‘50 mg QID
2 64/F Acute myeloblastic 103.6 Prednisone Complete NO
leukemia 20mg daily
3 59/M Hodgkin’s disease, 102.6 Prednisone Complete No
Stage IV 2Omg TID
4 71/F Chronic granulo- 103.6 Dcxamethasone Complete Partial
cytic leukemia 1.5mg BID
in blastic crisis
5 46/F Stomach cancer 103.0 Methyl Complete Partial
with intra- prednisolone
abdominal 50mg daily
carcinomatosis
6 71/M Multiple myeloma 101.0 Prednisone Complete Complete
20mg TID
7 60/M Chronic lympho- 102.0 Prednisone Complete Complete
cytic leukemia, 50mg TID
Stage IV
8 46/M Acute non-lympho- 103.4 Methyl Complete Complete
cytic leukemia prcdnisolone
I OOmg daily
9 60/F Hodgkin’s disease 101.8 Prednisone Complete NO
Stage IV-B 20mg BID
I0 55/F Myclodysplastic 104.0 Prednisonc Complete No
syndrome 2Omg BID
II 70/M Hodgkin’s disease 102.0 Prcdnisone Complete (:omplcte
Stage IV-B 4Omg BID
12 73/F Non-Hodgkin’s 103.2 Dexamethasonc Complete” Complete
Lymphoma 40mg TID
Stage IV

*Initially no response with naproxen 250mg BID but complete response with 375mg BID

Thus, naproxen resulted in complete lysis of especially in these immunocompromised pa-

fever in 90% of patients with neoplastic fever tients. Naproxen is established in the manage-
and corticosteroids in 50%. Figure 1 illustrates ment of neoplastic feveP”‘. Recent study has
the case of a patient with stage IV-B Hodgkin’s shown that it may be useful in the differential
disease who had a prompt, complete lysis of diagnosis of fever of undetermined origin in
fever with naproxen, but no lysis of fever with cancer patients’,‘“.‘“-“. The use of a modest dose
prednisone at a dose of 20 mg three times per for a short-term duration suppresses neoplastic
day. fever completely and promptly in almost all pa-
tients with neoplastic fever, but has no anti-
pyretic effect on infectious fever7,“1.17. Lysis of
Cornmmt neoplastic fever has been also observed with
Neoplastic fever, which occurs in cancer pa- another non-steroidal anti-inflammatory agent,
tients in absence of infection or other causes, indonlethacin’X-‘!‘, and also with an unrelated
is not uncommon and is usually encountered drug, cycloheximide”“.
in advanced neoplastic diseases and hemato- Corticosteroids are also known for fever-
logic malignancies ‘I-“,. In clinical practice, it is suppressing effects in both non-neoplastic and
often a troublesome problem due to the need neoplastic fevers. For example, a rapid defer-
to repeatedly exclude an infectious etiology, vescence has been often observed in neoplastic
144
fever associated with Hodgkin’s disease when
prednisone is administered as part of combi-
nation chemotherapy. Similar to naproxen, the
lysis of fever induced by corticosteroids occurs
within 12 hours and normal temperature is sus-
tained while receiving the drugs.
The mechanisms by which naproxen and cor-
ticosteroids induce lysis of neoplastic fever are
unknown. It is likely that the mechanisms are
different, given that naproxen has a selective
antipyretic activity against neoplastic fever while
the corticosteroids have effects on infectious
fever as well. Studies on the antipyretic effects
of naproxen and corticosteroids may provide
a light in the understanding of the pathogen-
esis of infectious and neoplastic fevers.
Although the corticosteroids induce fever
lysis, the present study suggests that naproxen
is a more effective and predictable antipyretic
agent in treatment of neoplastic fever. A well-
designed prospective study is recommended to
confirm this observation.
Acknowledgements
The author would like to acknowledge the
partial support of the Oncology Fund of the
Samaritan Foundation, Dayton, Ohio.
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