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Chemotherapy induced vomiting
(CIV) has been shown to have a detrimental influence
on quality of life and treatment compliance of
patients [1]. Despite the use of novel anti-emetics,
breakthrough CIV can occur in 30-40% of children
receiving moderate or highly emetogenic chemotherapy
(MEC/HEC) [2,3]. There is paucity of data regarding
choice of optimum agent and management of
breakthrough CIV in children [3]. The present study
was planned to demonstrate efficacy and safety of
olanzapine in the treatment of breakthrough vomiting
in children receiving MEC or HEC.
This observational study was
conducted over a period of 6 months in children aged
2-18 years, receiving MEC or HEC who developed
breakthrough emesis on protocol-defined prophylaxis,
as described previously [4]. Institutional ethics
committee approval and written informed consent from
parents were obtained. The dose of oral olanzapine
was 0.05-0.1 mg/kg/dose (maximum 5 mg/dose) once in
every 24-hour period for 3 days, regardless of
duration of chemotherapy block or subsequent
response. The dose was rounded off to the closest
half or full tablet of commercially available
preparations of 2.5 mg and 5 mg strengths.
Laboratory investigations included complete blood
count, liver and kidney function at screening and
before each cycle. Each episode of vomiting and
treatment related adverse events like sedation and
transaminitis were recorded as per the Common
terminology criteria for adverse events ver 4.03,
for atleast 5 days [5].
The primary outcome was an
assessment of response for 5 days from the first
dose of olanzapine. Complete response (CR) was
defined as no emetic episode and use of no other
rescue medications. Partial response (PR) was if
patient had 1-2 emetic episodes with no use of
rescue medications, and failure (refractory) if
patient had more than 2 emetic episodes and/or use
of rescue medications. Rescue drugs were permitted
as per physician’s discretion (commonly
metoclopramide). Data were analyzed using IBM SPSS
version 23.0, using standard physician’s statistical
methods.
During the study period, 108
(median age 9.2 years) pediatric cancer patients
received 412 blocks of MEC and HEC. A total of 31
(31.8%) patients and 42 (10.1%) chemotherapy blocks
were associated with breakthrough emesis. Eleven
patients had breakthrough emesis in more than one
block. Demographic data of patients is shown in
Table I. The mean (range) olanzapine dose
was 0.09 (0.04-0.15) mg/kg/dose.
Table I Demographic Characteristics of the study Population (N=31)
| Characteristic |
(%) |
| Male |
21 (68) |
| Age <10 years |
18 (58) |
| Type of
malignancy |
|
Hematological |
17 (54) |
|
Solid Tumor |
14 (45) |
| Disease
status |
| Standard
risk/Non metastatic |
19 (61) |
| High
risk/metastatic |
12 (39) |
| Emetogenic
potential |
| Moderate |
14 (45) |
| High |
17 (54) |
|
Cisplatin regimes |
5 (16) |
|
Dexamethasone |
29 (93) |
|
Intrathecal drug |
14 (45) |
|
Chemotherapy schedule |
| Single day |
05 (16) |
| Multiple day |
26 (84) |
Complete and partial responses
were observed in 34 (80.9%) and 6 (14.3%)
chemotherapy blocks, while 1 (2.4%) patient had
refractory vomiting. One patient did not receive the
drug after first dose and was not included in
response assessment. The mean (SD) dose of
olanzapine in patients with CR was 0.09 (0.02)
mg/kg/dose and in PR was 0.08 (0.02) mg/kg/dose,
P=0.68. There was no statistical difference in
CR rates based on age (<10/>10 years, P=0.23),
gender (P=0.68), emetogenic regimen (MEC/HEC,
P=1.0) or single/multiple-day chemotherapy (P=0.2).
The most commonly reported adverse events were grade
I-II sedation in 9 patients (11 chemotherapy blocks)
and increased serum transaminase levels in 3
patients (3 chemotherapy blocks). Olanzapine was
discontinued in one patient due to orthostatic
hypotension. The mean (SD) olanzapine dose in
patients who had and did not have sedation was 0.11
(0.022) and 0.08 (0.001) mg/kg/dose, respectively;
odds ratio 1.17, (95% CI: 1.08-1.27, P=0.0001).
It is recommended to use an antiemetic with a
different mechanism of action, for the treatment of
breakthrough vomiting, than that used for
prophylaxis [6]. A CR rate of 57% with an overall
response of 86% has been reported earlier in a
retrospective study on 20 subjects [7]. Our study
was pros-pective in nature with pre-defined
anti-emetic prophylactic protocols and indications
for olanzapine use. We believe, this led to a more
accurate and early use of olanzapine, resulting in
better control of CIV and higher CR rates. Two
studies in adult patients report similar results,
CR, 70% and 61% respectively [8,9].
The most common side effects
reported are sedation, transaminitis and weight gain
[7-9]. Significant weight gain was not expected as
the duration of treatment with olanzapine for
refractory CIV is short. Flank, et al.,
reported sedation in 7%, and it was significantly
associated with higher olanzapine dose, as also
observed in our study [7].
The results of this study,
despite small sample and lack of controls, suggest
olanzapine as an effective anti-emetic drug for
breakthrough CIV. Its low cost, oral formulation and
safety profile are of added value in cost-constraint
settings.
Disclosure: Presented as a
poster in PHOCON 2018.
Contributors: NT, SK: data
acquisition, analysis, drafting manuscript, agree
with final version; SJ: data analysis, reviewing
manuscript, agree with final version; GK: concept
and design, data analysis, reviewing manuscript,
agree with final version.
Funding; None; Competing
interest: None stated.
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