Annals of Oncology 7: 587-592, 1996.
O 1996 Kluwer Academic Publishers. Printed in the Netherlands.
Original article
A randomised placebo controlled study with ondansetron in patients
undergoing fractionated radiotherapy
L. Franzen,1 J. Nyman,2 H. Hagberg,3 M. Jakobsson,4 B. Sorbe,5 A. L. Nyth,6 H. Lomberg6
& R. Henriksson1
Departments of Oncology, University Hospitals ofiUmed, 2Goteborg, 3 Uppsala, *Linkoping, 5Orebro, and 6Glaxo-Wellcome, Sweden
the placebo group (P < 0.01). Patients given ondansetron had
fewer days with emesis and nausea compared with placebo
Background: There are few randomised studies comparing (P < 0.05). The mean sum score of patients weekly grading of
anti-emetic drugs for the prevention of nausea and vomiting symptoms showed that the ondansetron group had less inin patients treated with fractionated radiotherapy. The aim of convenience than the placebo group (P < 0.05). This differthe study was to compare the anti-emetic efficacy of 8 mg ence persisted during the first three weeks, but not thereafter.
Similarly, some quality of life measures showed significant
dose ondansetron twice a day with placebo.
Materials and methods: One hundred eleven patients who differences in favour of the ondansetron group. More pawere to commence a course of 10 or more daily fractionated tients (n - 13) withdrew due to lack of efficacy in the placebo
radiotherapy including the abdomen were included in the group compared with patients (n — 8) in the ondansetron
study. The patients recorded daily emesis, nausea and bowel group.
habit and graded weekly symptoms of nausea, vomiting, diarConclusions: The present study illustrates that prophylacrhoea and lack of appetite. The EORTC C30 questionnaire tic anti-emetic administration of ondansetron is effective in
was completed.
preventing nausea and vomiting in patients undergoing fracResults: 67% of patients given ondansetron had complete tionated radiotherapy of the abdomen.
control of emesis compared with 45% of patients with placebo (P < 0.05). The number of emetic episodes recorded on Key words: diarrhoea, emesis, fractionated radiotherapy,
the worst day was 1.4 for the ondansetron group and 3.1 for ondansetron, quality of life
Summary
Introduction
Materials and methods
Radiotherapy of malignancies in the abdomen induces
nausea and vomiting in a significant number of patients.
The frequency intensity varies depending on the dose
schedule, and the irradiated volume [1, 2]. Current
available anti-emetics (e.g., metoclopramide, nabilone,
chlorpromazine or levonantradol) [3, 4] have been
shown to control these problems in about 50% of patients. However, these drugs are regularly associated
with sedation and extrapyramidal sensations partially
due to interaction with dopamine receptors [5]. Ondansetron, a selective 5-hydroxytryptamine 3 receptor
(5-HT3) antagonist is devoid of dopamine receptor
interaction [6, 7] and has been suggested to reduce the
radiation-induced emesis [8, 9]. The present paper describes the results from a multicentre randomised,
double-blind, placebo-controlled study including 109
patients given fractionated radiotherapy to the abdomen.
Patients and irradiation
This was a multicentre, double-blind, randomised, parallel-group
study design. Males and females, aged at least 18 years, who were to
commence a course of 10 or more daily fractionated megavoltage
radiotherapy treatment were included in the study. A total of 111
patients were recruited, 54 patients were randomised to receive
ondansetron and 57 patients to the placebo group. Two groups of
patients were included, a group of patients with non-gynaecological
malignancies (n — 88) and a group of gynaecological malignancies
(n — 23). Each group was randomised in four strata depending on
which part of the abdomen the radiotherapy treatment was focused
and the presence or absence of previous history of nausea/emesis
during earlier cancer therapy treatment. The intent-to-treat population was defined as all patients randomised to treatment who fullfilled the inclusion criteria and were given the study medication
(Table 1). Exclusions criteria were: concurrent chemotherapy, severe
concurrent illness other than neoplasia disease, gastrointestinal
obstructions, CNS-metastases, vomiting or anti-emetic treatment in
the previous 24 hours, administration of benzodiazepines except for
night sedation or administration of anu'-inflammatory steroids. Randomisation of treatment was computer-generated using SAS-Ran-
588
Table 1. Primary tumour site (intent-to-treat population).
Ondansetron
Placebo
Total
Gastrointestinal
Genito-urinary
Gynaecological
Haematopoietic/immunological
4
27
10
12
3
27
12
14
7
55
22
26
Total
53
56
109
dom Number Functions with treatment sequences balanced in
blocks of two patients. Two randomised patients, one in each group,
were excluded from the intent-to-treat population, because one
patient randomised to placebo only received one fraction of radiotherapy and one patient randomised to ondansetron was on antiemetic treatment prior to study entry due to severe nausea and
vomiting. Informed consent was obtained individually from each
patient and the study was approved by the ethical committees for
each of the five participating centres.
In the non-gynaecological patients one treatment field had to be
more than 90 cm2, located between the level of upper border of the
11th thoracic vertebra and the lower border of the 2nd lumbar vertebra. A minimum dose of 1.7 Gy per fraction at the mid-plane of
the volume was required. In the gyneaecological patients, whole
abdominal or pelvic fields were included. The whole abdominal and
the lower abdominal fields were given by parallel open field technique. The dose per raction was 1.0 Gy for whole abdominal fields,
1.7 for lower abdominal fields and 2.0 for pelvic fields.
Drug administration
Ondansetron, 8 mg or placebo was administered orally twice a day
from the first day of irradiation until up to two days following the
last radiation treatment. The two different tablets were blinded for
the patient and the investigator. There was no difference in taste
between the two preparations. No other anti-emetic therapy was
allowed 24 hours prior to the start of or during the study. All other
concomitant medication was recorded. Each patient was provided
with rescue antiemetic medication, 10 mg metoclopramide tablets if
he/she experienced severe nausea/emesis on one day.
Evaluation
For comparison of proportions between the two groups Fisher's
exact test was used. For all other comparisons Fisher's nonparametric permutation test [11] was used. Confidence intervals for
proportions and means within the treatment groups, as well as differences of proportions and means between the two groups were
calculated.
Results
The radiotherapy treatment was similar in the study
groups with respect to the total radiated field size, dose
per fraction and the total number of fractions (Table 2).
Two patients in each treatment group had a treatment
field size < 90 cm2 between 11th thoracic and 2nd lumbar vertebra. The study period included at most the
first five weeks of each patients radiotherapy treatment
course. In total, the mean number of radiotherapy fractions administered to both groups was 18 with a range
of 12-25 fractions for the patients in the ondansetron
group and 8-25 fractions in the placebo group. The
mean number of radiotherapy fractions per week was
4.2 SD 0.5 in the ondansetron group, and 4.1 SD 0.6 in
the placebo group. Most of the patients (80%) were
treated on an out-patient basis.
Data were missing for the following assessments:
Table 2. Radiotherapy treatment and primary tumour site.
Ondansetron
Non-gynaecological
Placebo
patients
Number
Dose per fraction (Gy)
Mean
SD
Range
Field size (cm2) (Thll-L2)
Mean
SD
Range
Field size (cm2) (total)
Mean
SD
Range
43
2.0
1.7-2.4
1.7-2.4
112
37
59-294
44
2.0
1.7-2.5
1.7-2.5
128
49
70-420
Nausea and emesis were recorded during the study. The patients
completed a diary card throughout the radiotherapy course includ304
311
ing weekends and recorded the number of vomits, retches, and
117
154
grade of nausea (none, mild, moderate or severe). The presence of
90-660
77-999
diarrhoea was also noted. Each week the patients also completed a
Gynaecological patients
questionnaire containing four questions aimed at measuring pa10
12
tient's perception of inconvenience of nausea, emesis, diarrhoea and Number
loss of appetite. An overall rating of the patient's sense of well-being Dose per fraction
Mean
1.9
1.9
was recorded. The answers to each question were given on a VAS0.2
0.3
scale (0 — non inconvenience and 100 — as bad as it could be). The SD
Range
1.0-2.0
1.0-2.0
EORTC QLQ-C30 questionnaire [10] was completed before the
2
start of the radiotherapy course, at two weeks and at the end of Field size (cm ) (total)
Mean
389
357
treatment. The QLQ-30 incorporates nine multi-item scales: five
211
131
SD
functional scales (physical, role, cognitive, emotional and social),
225-999
Range
240-936
these symptoms scales (fatigue, pain, and nausea, and vomiting) and
a global health and quality-of-life scale.
All patients
Patients who took rescue-medication were considered treatment Number
53
56
failure each day it was taken. Patients who were withdrawn due to No. of fractions
lack of efficacy were assigned a non-zero value from that day on18
Mean
18
wards to the end of the radiotherapy treatment course when propor4
SD
4.5
tion of emesis/nauea days were compared. Patients who were
Range
12-25
8-25*
withdrawn due to other reasons were only evaluated up to the day of
withdrawal. The number of rescue-tablets taken and the time to first * One patient received eight radiotherapy fractions but were inrescue-medication was compared between treatments.
cluded in the intent-to-treat analysis.
589
1. Daily Diary Card: The first week diary card was (n - 8) in the ondansetron group. The patients in the
missing for one patient. However, the weekly as- placebo group were withdrawn earlier after a mean of
sessment (symptoms questionnaire) was per- four fractions (range 1-7) compared with the patients
formed. The patient was excluded at the first fol- in the ondansetron group who were withdrawn after a
low-up due to lack of compliance.
mean of 10 fractions (range 5-16) (P < 0.01).
2. Symptoms Questionnaire: The following weekly
Additionally seven patients given ondansetron were
assessments were missing for the ondansetron
group; baseline (n = 1) and the last week assess- Table 4. Distribution of patients with respect to the proportion of
ments (n = 7). For the placebo group the corre- days with emesis.
sponding figures were: week one assessment
Proportion of
Ondansetron
Placebo
(n — 1) and the last week assessments (n = 7).
days with
3. QLQ-C30: The following QLQ assessments for emesis
No. of
CumulaNo. of
Cumulathe ondansetron group were missing: the baseline
patients
tive (%)
patients
tive (%)
(n — 1), at study completion (n — 5) or earlier at
withdrawal (n -= 2). For the placebo group the
35 (67)
67
25 (45)
45
corresponding missing data were: baseline assess- 0
0.01-0.20
8(15)
82
13 (23)
68
ment (n — 1), at study completion (n = 3) or ear- 0.21-0.40
2(4)
86
73
3(5)
lier at withdrawal (n - 2).
0.41-0.60
92
1(2)
75
3(6)
2(4)
Sixty-seven percent of patients receiving ondanse- 0.61-0.80
96
2(4)
79
2(4)
100
12(21)
100
tron experienced complete control of emesis with no 0.81-1.0
emetic episodes, compared with 45% of patients receiving placebo (P< 0.05, 95% confidence intervals Patients who were rescued or withdrawn due to lack of efficacy were
(CI) 4% to 41%) (Table 3). The corresponding figures assigned a non-zero value from that day onwards. Patients withfor major emetic response, i.e., 0-2 emetic episodes, drawn due to other reasons were only evaluated up to the day of
were 85% and 61% for the two study groups, respec- withdrawal.
tively (P< 0.01, 95% CI for the differences 8% to
40%). After the first five fractions 96% of the patients Table 5. Nausea grade on worst day.
in the ondansetron group had complete or major reOndansetron
Placebo
sponse as compared with 70% in the placebo group Nausea
— no. of patients (%) —
(P < 0.01,95% CI 13% to 40%).
The mean number of emetic episodes on the worst
Total study period
day was 1.4 (SEM 0.5) in the ondansetron group comNone
9(17)
5(9)
pared to 3.1 emetic episodes (SEM 0.7) in the placebo
16 (29)
19 (37)
Mild
P- 0.075
Moderate
13 (25)
15 (28)
group (P < 0.05). In total, the mean proportions of days
11 (21)
20 (36)
Severe
with emesis were 0.13 (SEM 0.04) in the ondansetron
group and 0.27 (SEM 0.05) in the placebo group (P < First five fractions
24 (46)
10(18)
None
0.05) (Table 4). There was no significant difference be18 (35)
22 (39)
Mild
tween the study groups regarding nausea grade on
Moderate
8(15)
12(21)
worst day (Table 5). However, the mean proportion of
2(4)
12(21)
Severe
days with nausea was significantly less in the ondansetron group: 0.38 (SEM 0.04) compared with 0.55 (SEM
0.05) in the placebo group (P < 0.05) (Table 6). There Table 6. Distribution of patients with respect to the proportion of
was no significant difference between the two groups days with mild, moderate or severe nause.
with respect to time to first rescue medication or numProportion of
Ondansetron
Placebo
ber of tablets taken.
More patients {n — 13) withdrew due to lack of effi- days with
No. of
CumulaNo. of
Cumulacacy in the placebo group compared with patients nausea
patients
tive (%)
patients
tive (%)
Table 3. Emetic response on worst day.
Response emesis
Total study period
Complete
Major
First five fractions
Complete
Major
Ondansetron
Placebo
— no. of patients (%) —
P-value
35 (67)
44 (85)
<0.05
<0.01
41 (79)
50 (96)
25 (45)
34 (61)
33 (59)
39 (70)
<0.05
<0.01
0
0.01-0.20
0.21-0.40
0.41-0.60
0.61-0.80
0.81-1.00
9(17)
15 (29)
7(13)
4(8)
6(12)
11(21)
17
46
59
67
79
100
5(9)
8(14)
10(18)
5(9)
8(14)
20 (36)
9
23
41
50
64
100
P<0.05.
Patients who were rescued or withdrawn due to lack of efficacy were
assigned a non-zero value from that day onwards. Patients withdrawn due to other reasons were only evaluated up to the day of
withdrawal.
590
withdrawn; five due to adverse event after a mean of 10 after 15 and 17 fractions each. Patients on ondansetron
fractions (range 4-18), and two patients were displayed more days without emptying the bowel, but
withdrawn at first follow-up due to lack of compliance. the difference was not significant.
Of the withdrawn patients with adverse events, three
The mean sum score of patients weekly grading of
events were considered unrelated or unlikely to be re- inconvenience of symptoms (nausea, emesis, diarrhoea
lated to the study drug (diarrhoea, two patients and and loss of appetite) showed that the ondansetron
gastro enteritis, one patient). Two events, headache and group experienced significantly less inconvenience than
skin reactions were considered almost certainly related the placebo group during the first three weeks (P<
and possibly related, respectively (Table 7). There was 0.05) (Figure 2). Thereafter no significant difference
no significant difference between the two groups with could be observed. Similarly some quality of life measrespect to time to first rescue medication, neither did ures showed significant differences in favour of the
the groups differ regarding the number of rescue tablets ondansetron group after two weeks but not at the end
taken.
of the treatment (Figures 3 and 4).
Ondansetron was also shown to reduce the frequence of diarrhoea. Patients treated with ondansetron
had fewer days with diarrhoea assessed as loose/watery Discussion
stools and/or loperamide consumption (Figure 1). The
effect was apparent in the three first weeks of the radio- The results of the present placebo-controlled randomtherapy course. Two ondansetron treated patients ter- ised study showed a marked beneficial prophylactic
minated the radiotherapy treatment, due to diarrhoea, antiemetic effect of ondansetron, on prevention of nausea and vomiting and improvement in quality of life
evaluated by the patients themselves. The worst day
Table 7. Reasons for withdrawal from treatment
analysis showed that 35/52 (67%) of patients given
Reasons
Treatment
ondansetron had complete control of emesis through
the study period compared with 25/56 (45%) receiving
Ondansetron
Placebo
placebo. The mean number of emetic episodes on the
worst day was 1.4 for the ondansetron group compared
Adverse event
0
with 3.1 for the placebo group. Moreover, patients
Lack of efficacy
13
Other'
2
0
given ondansetron had fewer days with nausea and
fewer days with emesis compared with placebo.
Total
13
15
The extent of nausea and vomiting following radio1
Two patients were withdrawn at first follow-up due to lack of therapy varies depending on the dose schedule, the
compliance, took rescue medication without nausea/vomiting prob- irradiated volume and the site of treatment. Approxilems, did not comply with diary card completion.
mately 80% of patients receiving single high-dose abOND
|
| PLACEBO
PLACEBC
(p-oo5|
(p-11115)
52 55
51 55
\ o o f patients
52 56
Week 1
50 48
43 41
No of patients
31
Week 2
Week 4
Week 3
(us)
(n s )
38 -14
24 24
18 20
Week
Week 5
Figure 1. Percentage (SEM) of days per week the patients had diarrhoea assessed as loose/watery stools and/or loperamide consumption. Patients withdrawn from the study were evaluated up to withdrawal.
Week :
Week •
\\ eek 4
Week <
Figure 2. The mean (SEM) sum score of patients weekly grading of
inconvenience of symptoms of nausea, emesis, diarrhoea and loss of
appetite (0 - no inconvenience, 100 - as bad as it could be).
Patients withdrawn from the study were assigned the score of
inconvenience at withdrawal for the remaining radiotherapy
treatment course.
591
recent study reported that approximately 40% of the
patients with no antiemetic prophylaxis experienced
emesis/nausea when undergoing fractionated radiotherapy [12]. In a subgroup of patients given antiemetic
prophylaxis due to high risk for developing symptoms,
approximately 50% developed symptoms despite the
prophylactic
treatment The most commonly used antip'<O.OI
emetic prophylaxis has been metoclopramide [12]. In
the present study, after five radiotherapy fractions, significantly more patients, 46%, were completely free
from nausea compared with only 18% in the placebo
group (P < 0.05). However, evaluating the total period,
no significant difference with regard to complete response against nausea was found.
The study of Priestman et al. [13] showed that ondansetron was significantly superior to prochlorperazine in preventing emesis and nausea caused by daily
fractionated radiotherapy treatments to the upper
abdomen. In that study the treatment period consisted
* Mean week 2.
b
The change in scores from pre-treatment to week 2.
of five or more daily fractions. There are few studies
Figure 3. EORTC QLQ C-30 symptoms scales and items. Mean comparing antiemetic drugs for fractionated radiotherand standard error at pre-treatment and week 2. Scores range from apy, but tropisetron, another 5-HT3 receptor antagonist
0 to 100 with a higher score representing a greater degree of symp- has shown beneficial result as antiemetic prophylaxis
toms.
during postoperative abdominal irradiation of ovarian
carcinoma patients [13]. Granisetron also a 5-HT3 receptor antagonist has shown good results in prevention of
OOndanselron pre-treatmeni
• Placebo pre-treatment
irradiation induced emesis for total body irradiation [14]
• Ondansetron w eek 2
and comparing the different 5-HT3 receptor antagonists
S Placebo week 2
there arenoconclusivedataifoneissuperiorovertheothers.
In this study patients given ondansetron reported
p'<0.05
better functioning, quality of life and lower symptom
levels at week 2 on the QLQ-C30 indicating a more
favourable effect of ondansetron in comparison with
placebo. Many of these aspects such as sleep disturbance
and appetite (see Figures 3 and 4) are of importance
for the patients during a radiotherapy treatment course.
Analysis based on patients' weekly grading of inconvenience of symptoms including vomiting, nausea, diarrhoea and lack of appetite showed that there was a
trend towards worsening of the symptoms with an increasing number of fractions and that the beneficial
effect of ondansetron was evident for up to three
weeks, after which significant differences were not
identified. However, it should be noted that in the present study approximately 50% of the patients completed
their radiotherapy treatment course within three to
" Mean week 2.
b
four weeks, resulting in reduced sample signs for the
The change in scores from pre-treatment to week 2.
Figure 4. EORTC QLQ C-30 functioning scales. Mean and stand- later comparisons. Whether this reflects patient selecard error at pre-treatment and week 2. Scores range from 0 to 100 tion or the appearance of additional stimuli during the
with a higher score representing a higher level of functioning.
later stage of long-term radiotherapy, remains to be
evaluated. Nevertheless, this is one of the very few studies
dominal radiotherapy of >600 cGy developed nausea that displayed an increased quality of life, evaluated by
and vomiting, whereas only 50% of patients with daily patients themselves, in patients treated with ondansefractionated doses of >180 cGy were affected [1, 2]. tron during fractionated radiotherapy. Comparing the
Although the nausea and emesis with daily fractionated functional scales (physical, role, cognitive, emotional
doses are less severe, the duration may be considerably and social) and the global quality of life there was a
longer since a course of radiotherapy may involve up to tendency in favour for the ondansetron group compar30-40 fractions over a 3-8-week period and if untreat- ed with placebo (Figure 4). The symptom scales (Figed these symptoms could persist over this period. A ure 3) showed differences for fatigue, nausea and vomOOndamHron pre-trailroent
• Placebo pre-treutment
• OndansHron w eeL 2
• Placebo week 2
592
iting and constipation but just minor differences for the
other studied parameters.
Patients given ondansetron reported lower levels of
diarrhoea than patients given placebo, supporting an
earlier open study [9]. In the present controlled study
patients treated with ondansetron had significantly
fewer days with diarrhoea assessed as loose/watery
stools and/or consumption of loperamide (Imodium*).
Patients' weekly grading of symptoms of diarrhoea indicated less inconvenience during the first three weeks of
radiotherapy but not thereafter.
An additional finding of the beneficial effect of
ondansetron was that the patients in the placebo group
were withdrawn earlier due to lack of efficacy
after a mean of four fractions compared with the
ondansetron group who withdrew after a mean of ten
fractions. It should be noted that no patients in the placebo group were withdrawn due to adverse event as
compared to five patients in the ondansetron group
who were withdrawn after a mean of ten fractions.
However, only one event was considered to be directly
drug related (headache). The other events were diarrhoea, gastro enteritis and skin reaction. Overall there
was good compliance among the patients. Only two patients were excluded at the first clinical assessment due
to lack of compliance, both treated with ondansetron.
In conclusion, it is evident that the selective 5-hydroxytryptamine 3 receptor antagonist, in this study
ondansetron, offers a new approach in managing radiotherapy-induced emesis. The present study demonstrated marked beneficial prophylactic antiemetic
effect of ondansetron during fractionated radiotherapy
of malignances in the abdomen. An improvement,
which was strengthened by the patients own evaluation
in quality of life. Furthermore, the well-known side
effect, constipation, seemed to be of clinical importance
in reducing diarrhoea during the radiotherapy treatment
course.
2. Priestman TJ, Priestman S. An initial evaluation of nabilone in
the control of radiotherapy-induced nausea and vomiting. Clin
Radiol 1984; 35: 265-6.
3. Priestman TJ, Priestman S, Canney PA. A double-blind randomised cross-over comparison of nabilone and methoclopramide in the control of radiation-induced nausea. Clin Radiol
1987; 38: 543-4.
4. Lucraft HH, Palmer MK. Randomised clinical trial of levonantradol and chlorpromazine in the prevention of radiotherapyinduced vomiting. Clin Radiol 1982; 33:621-2.
5. Rawlins MD, Taylor WB, Bateman DN. Rational approaches
to therapy for nausea and vomiting. Two common solutions. In
Davis, CJ, Lake-Bakaar GV, Grahame-Smith DG (eds): Nausea
and Vomiting: Mechanism and Treatment. Berlin, Heidelberg:
Springer-Verlag 1986; 167-71.
6. Butler A, Hill JM, Ireland SJ et al. Pharmacological properties
of GR38032F, a novel antagonist at 5-HT3 receptors. Br J
Pharmacol 1988; 94: 397-412.
7. Gunning, Hagan RM, Tyers BM. Cisplatin induces biochemical
and histological changes in the small intestine of the ferret Br J
Pharmacol 1987; 90:135.
8. Priestman TJ. Clinical studies with ondansetron in the control
of radiation-induced emesis. Eur J Cancer Clin Oncol 1989;
25:829-33.
9. Henriksson R, Lomberg H, Irsaelsson G, Franzen L. The effect
of ondansetron on radiation-induced emesis and diarrhoea.
Acta Oncol 1992; 31: 767-9.
10. Aaronson NK, Ahmedzai S, Bergman B et al. The European
Organization for Research and Treatment of Cancer QLQC30: A quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365-76.
11. Bradley JV. Distribution-Free Statistical Test. London: Prentice-Hall Inc. 1968; 78-80.
12. Feyer PC. Incidence of emesis and nausea in fractionated
radiotherapy patients. Glaxo Ondansetron Satellite Symposia.
Advances in Optimising the Control of Emesis, 20 November
1994, ESMO, Lisbon, Portugal.
13. Priestman TJ, Roberts JT, Upadhyaya BK. A prospective randomised double-blind trial comparing ondansetron versus
prochlorperazine for the prevention of nausea and vomiting in
patients undergoing fractionated radiotherapy. Clin Oncol
1993; 5: 358-63.
14. Sorbe B, Berglind BM, de Bruijin K. Tropisetron, a new 5-HT3
receptor antagonist, in the prevention of radiation-induced
emesis. Radiother Oncol 1992; 23(2): 131-2.
15. Prentice HG, Cunningham S, Gandhi L et al. Granisetron in
the prevention of irradiation-induced emesis. Bone Marrow
Transplant 1995; 15(3): 445-8.
Acknowledgement
This study was supported by Glaxo Wellcome AB,
Sweden.
References
1. Danjoux CE, Rider WD, Fitzpatric PJ. The acute radiation
syndrome. A memorial to William Court-Brown. Gin Radiol
1979; 30: 581-4.
Received 22 February 1996; accepted 7 June 1996.
Correspondence to:
Lars Franzen, MD, PhD
Department of Oncology
University Hospital
S-901 85 Umei
Sweden