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Brief Reports
Comparison of Dexamethasone
and Metoclopramide as Anti-
emetics in Children Receiving
Cancer Chemotherapy
Maheboob Basade
S.S. Kulkarni
A.K. Dhar
P.S.R.K. Sastry
B. Saikia
S.H. Advani
Nausea and emesis following
chemotherapy are often reported by
patients. The commonly used standard
antiemetic drugs such as
metoclopramide(l), prochloperazine(2) and
dexamethasone(3) have been demonstrated
to be only moderately effective in
controlling these symptoms. Recently
newer 5-HT
3
receptor antagonists like
ondansetron(4) and granisetron(5) have
been used in controlling emesis.
The aim of present study was to
compare the efficacy and safety of
dexamethasone versus metoclopramide in
prevention of nausea and emesis in
children receiving cyclophosphamide
based chemotherapy as outpatients.
Subjects and Methods
From December 1993 to February
1994, we enrolled children (<15 years)
with malignancies receiving
cyclophosphamide based chemotherapy as
From the Department of Medical Oncology, Tata
Memorial Hospital, Bombay 400 012.
Reprint requests: Dr. S.H. Advani, Chief,
Department of Medical Oncology, Tata Memo-
rial Hospital, Parel, Bombay 400 012,
Received for publication: June 17,1994;
Accepted: May 29,1995
outpatient at Tata Memorial Hospital,
Bombay. We used a randomized, single
blind, cross-over trial in which every
patient would be control of his own. During
two consecutive courses of same
chemotherapeutic drugs, each patient
received either dexamethasone (8 mg/m
2
IV slowly 15 minutes prior to
chemotherapy) or metoclopramide (1.5
mg/kg IV 15 minutes prior to
chemotherapy). During the next cycle,
patients received the alternate treatment
protocol. In order to assess response,
patients were called next day and asked
about nausea, emesis or any other side
effects. Nausea was graded as: complete
response (no nausea or looking not at all
sick), moderate (tolerable, interference with
activity or looking more sick) and severe
(intolerable, bed ridden for over 2 hours or
looking very much sick)(6,7). Emesis was
graded according to number of emetic
episodes: complete response (none), major
response (1-2 episodes), minor response (3-
4 episodes) and failure (> 5 episodes)(6,7).
Possible side-effects of drugs like dystonia,
insomnia, elated mood, depression, lack of
appetite, abdominal discomfort and head-
ache were also noted. The first author
(M.B.) assessed the response for nausea
and emesis.
Results
Twenty seven children receiving a total
of 53 chemotherapeutic cycles were
entered in this study. Of twenty seven, 26
children were in Group A receiving
dexamethasone and 27 were in Group B
receiving metoclopramide. One patient
from Group B could not complete the
cross-over trial. Clinical characteristics of
patients are shown in Table I. All patients
received intravenous cyclophosphamide in
dose of 600 mg/m
2
or more along with
other drugs like doxorubicin, vincristine
and prednisolone.
Complete response for emesis in Group
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A was significantly greater than Group B
(16 vs 8, p <0.02), while for nausea
complete response in Group A was 15
while in Group B it was 7 (p<0.02). Major,
minor responses or failure for emesis (3 vs
6, 3 vs 7, 4 vs 5) and for nausea were (4 vs
5, 4 vs 4,3 vs 10) in Group A and B
respectively. Side-effects were minimum.
Dystonia (one case in Group B), insomnia
(one case in Group A), depression (one
case in Group A, 3 in Group B), lack of
appetite (one in Group A, 4 in Group B),
abdominal discomfort (one in Group A, 2
in Group B) and headache (one case in
Group B) were seen.
Discussion
Antiemetics previously used to control
nausea and emesis induced by
chemotherapy include high dose
metoclopramide(l) and
prochlorperazine(2). They have limitations
like sedation and extraphyramidal
reactions. Methylprednisolone was first
used as an antiemetic in 1980(8). This was
followed by the use of dexamethasone in
various studies in various doses as an
antiemetic(3,7,9).
TABLE I-Patient Characteristics
No. of patients
Randomized 27
Evaluable 26
No. of chemotherapeutic cycles 53
Age (years)
Range 3-14
Median . 7
Boys: Girls 21: 6
Type of cancer
Ewing's sarcoma 8
Non Hodgkin's lymphoma 8
Hodgkin's disease 6
Rhabdomyosarcoma 3
Retinoblastoma 1
Acute lymphoblastic leukemia 1
This randomized, single blind, crossover
design eliminated a number of inherent
drawbacks in comparing one drug with
another. Since each patient received the
same chemotherapeutic agents in same
doses for both cycles of chemotherapy,
both dexamethasone and metoclopramide
were tested against the same emetic
stimuli.
Our results demonstrate the better
efficacy of dexamethasone and its
superiority over metoclopramide in
alleviating the nausea and emesis when
used before administrating
cyclophosphamide based chemotherapy.
Dexamethasone administration caused no
major side effects and was tolerated quite
well. Addition of dexamethasone to 5-HT
3
receptor antagonists has been shown to
increase antiemetic efficacy as compared to
when used alone(l0). Although, the exact
mechanism of action of dexamethasone as
an antiemetic is not known, few hypotheses
have been put forward. Corticosteroids
may act on the activated prostaglandin
pathway(8). They may act on the
chemoreceptor trigger zone either by
modifying capillary permeability(11) or by
stabilizing the membrane or intracellular
components and may have a role in
endorphin release(12).
Thus we conclude that dexamethasone
is effective in preventing nausea and
emesis following cyclophosphamide based
chemotherapy. Its antiemetic activity
appears to be superior to metoclopramide.
Further studies are needed to determine the
optimal dosage schedule of dexamethasone
either alone or in combination with others.
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