A Randomized Cross-over Trial of Granisetron and Dexamethasone ...

This study was a single-blind, randomized, twoperiod
two-treatment cross-over trial. Patients with
non-small cell lung cancer received cisplatin
[80 mg/m 2 intravenously (i.v.)] on day 1, and
vindesine (3 mg/m 2 i.v.) on days 1 and 8, with or
without mitomycin C (8 mg/m 2 i.v.) on day 1.
Those with small cell lung cancer received cisplatin
(80 mg/m 2 i.v.) on day 1, and etoposide
(100 mg/m 2 i.v.) on days 1-3. Cisplatin was administered
by 1-h drip infusion with 2.5 to 3 liters
of hydration.
Patients were randomly assigned to receive either
GRN + DEX: GRN (40/tg/kg) diluted in 100 ml of
normal saline given i.v. 30 min before 4 h after
cisplatin infusion, and DEX (16 mg i.v.) 30 min before
cisplatin infusion, or GRN alone at the same
doses as those described above. The two fixed
doses of granisetron were administered to all patients
to avoid any influence of differing drug
doses. All patients were given MET (40 mg) diluted
in 100 ml of normal saline i.v. over 30 min
twice daily on days 2-5, and DEX (8 mg i.v. on
days 2 and 3, and 4 mg on days 4 and 5). They
were crossed over to the other antiemetic regimen
on their second course of chemotherapy.
All patients were requested to record the severity
of nausea using a graded scale (none, mild,
moderate, or severe) and a visual-analogue scale
(VAS; 0 = no nausea, 100 = intolerable nausea), the
number of episodes of vomiting, and side effects
on a diary card on days 1-5. Complete response
(CR) was defined as absence of vomiting episodes
and none on the graded scale of nausea.
Patients were considered evaluable for efficacy if
they received both courses of antiemetic therapies.
Mean values of VAS for nausea and the number of
emetic episodes for each of the two regimens were
calculated. The sample size was determined on the
assumption that the CR rate on day 2 for GRN
alone and that for GRN + DEX were 20 and 40%,
respectively. With a power (1-6) of 80%, the estimated
required sample size was 40 patients. 8 ' The
cross-over difference (the difference between the
two regimens) and its statistical signficance was examined
by the Hills-Armitage method, which is
based on Student's t test. The statistical significance
of patient preference was examined by McNemar's
test. 9 '
Results
Between May 1993 and April 1994, 40 patients
were entered into the study. Nine patients were not
evaluable for efficacy. One of them could not be
given DEX because of aggravation of diabetes mellitus.
The other 8 patients received only one course
of chemotherapy: seven because of disease progres-
DEXAMETHASONE FOR DELAYED EMESIS
Table I. Characteristics of Evaluable Patients
Characteristics
GRN + DEX
then
GRN alone
Number of patients 16
Median age (range) 56.5 (39-71)
Male/Female
10/6
Chemotherapy regimens
cisplatin + vindesine
cisplatin + vindesine +
8
mitomycin C
7
cisplatin + etoposide 1
GRN alone
then
GRN + DEX
15
65.0 (22-77)
10/5
sion, and one because of impaired renal function.
The characteristics of 31 evaluable patients who
completed both courses of antiemetic therapy are
summarized in Table I. There was significant difference
between the two antiemetic treatment groups.
Of the 31 patients, 26 were fully evaluable. Two
patients were evaluable only for the number of
emetic episodes from their medical records because
their diary cards were lost. The other 3 patients
were included only in the assessment of the CR
rate, because they were unable to fill out their
diary cards due to severe vomiting.
Nausea was assessed in 26 patients. As shown in
Fig. 1, the VAS scores on days 1 and 2 for
GRN + DEX were lower than those for "GRN alone,
though statistical significance was obtained only on
day 2 (P