Hospital Pharmacy - June 2020 - 179

179

Sada et al
= 0.84), whereas non-aspirin NSAIDs (OR 1.23, 95% CI =
0.95-1.64; SUCRA = 0.26) were ranked low for safety.
High-dose aspirin (≥300 mg/d) was comparable with lowdose aspirin (≤160 mg/d) in efficacy (OR 1.12, 95% CI =
0.59-2.10; SUCRA = 0.58) but had an inferior safety profile (SUCRA = 0.51).41
An animal control study was divided into 9 different
groups having 5 animals in each group: Group 1: Control
Group (animals were kept on normal diet and water), Group
2: Control Group + vehicle treated (1 mM EDTA saline subcutaneously) in a weekly injection and 0.5% carboxymethyl
cellulose sodium salt orally daily, Group 3: DMH treated
(DMH weekly at a dose of 30 mg/kg subcutaneously), Group
4: DMH + celecoxib 6 mg/kg was co-administered orally
daily, Group 5: DMH + etoricoxib 0.6 mg/kg was co-administered orally daily, Group 6: DMH + diclofenac 8 mg/kg
was co-administered orally daily, Group 7: celecoxib daily at
a dose of 6 mg/kg orally, Group 8: etoricoxib 0.6 mg/kg
orally daily, Group 9: diclofenac 8 mg/kg orally daily. This
study showed that a number of aberrant crypt foci, a group of
atypical tube-like glands in the lining of colon, were minimum in DMH + celecoxib, DMH + etoricoxib, and DMH
+ diclofenac groups, whereas they were maximum in DMH
group. It also suggested that when co-administered with
DMH, celecoxib, etoricoxib, and diclofenac were found to
regress the COX-2 expression, which was otherwise overexpressed in DMH-treated group.52
Paeonol inhibits human CRC cell proliferation, induces
cell apoptosis, and downregulates the expression of COX-2
in CRC cells in a dose-dependent manner. After treating the
3 human CRC cell lines with 30 mg/L paeonol, the viability
of cells was assessed by MTT assay from 24 to 72 hours, and
the proliferation of these cell lines was significantly inhibited, especially in the LoVo cells. The percentage of apoptotic cells treated with paeonol was significantly higher
(increased from 15.4% to 38.6%) compared with that in the
control group (P < .01), indicating that paeonol may inhibit
the growth of CRC cells by inducing apoptosis. The expression of COX-2 in cells treated with 30 mg/L paeonol was
observed to be lower than that in the control group. Treatment
with 120 mg/L paeonol led to a further decrease, which indicates a dose-dependent decrease in COX-2 expression.53
Indomethacin was found with protective effect in CRC.
Lönnroth and colleagues54 reported that the stem cell master
regulator SOX2 was increased by NSAIDs (P < .01), as well
as the tumor suppressor miR-630 (P < .01), whereas BMP7,
a marker for poor prognosis in CRC, was downregulated by
NSAIDs (indomethacin; P < .02).

Conclusions
Long-term use of aspirin is associated with reduction in
adenoma recurrence, reduced mortality, and increased disease-free and OS. The benefit is significant in the patients
with strong COX-2 expression. Globally, some data seem to

suggest that aspirin use may improve the clinical outcome of
patients with metastatic CRC receiving CT. Moreover, it
has been suggested that a potential synergic activity may
exist for concomitant aspirin use and capecitabine-based
treatment. Factors such as smoking and alcohol drinking
reduce the benefit of aspirin use in the CRC. Even though
some literature recommends low-dose aspirin over highdose aspirin, further study is needed to arrive at a clear
conclusion regarding the most beneficial dose of aspirin.
The use of selective COX-2 inhibitors both prior to and
after diagnosis of CRC seemed to be mildly associated
with the reduction in mortality of patients with CRC. This
survival benefit was also shown in patients diagnosed with
rectal cancer or those undergoing OP followed by CRT
within 180 days after diagnosis. Some literature state that
COX-2 inhibitors might play a synergistic role in adjuvant
CT of FOLFOX regimen. Celecoxib was found to increase
the radiosensitization of colon cancer cells. High-dose
celecoxib (400 mg twice a day) was associated with better
outcome than low-dose celecoxib (200 mg twice a day).
The use of rofecoxib is associated with reducing the risk
of CRC; however, it is associated with cardiovascular risk
and it is not recommended to use it for the prevention of
CRC. It is currently withdrawn from the market due to its
side effects.
Among individuals with previous colorectal neoplasia,
non-aspirin NSAIDs are the most effective agents for the
prevention of advanced metachronous neoplasia, whereas
low-dose aspirin has the most favorable risk:benefit profile.
One study states that ibuprofen is associated with reducing
inflammatory mediators. Further control study is needed in
this area to come up with clear-cut point with the use of
NSAIDs in the CRC.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

1.
American Cancer Society (ACS). Colorectal Cancer
Screening* (%), in adults 50 years and older. Color Cancer
Facts Fig 2017-2019. 2017:1-40.
2. Marley AR, Nan H. Epidemiology of colorectal cancer. Int J
Mol Epidemiol Genet. 2016;7(3):105-114.
3. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal Cancer
Statistics. CA Cancer J Clin. 2017;67(3):177-193.

4.
Longo DL. Colorectal adenomas. N Engl J Med.
2016;374(11):1065-1075.
5. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal
A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-691.

Hospital Pharmacy - June 2020

Table of Contents for the Digital Edition of Hospital Pharmacy - June 2020