Are chemotherapy drugs effective in treating colorectal cancer?

Inclusion criteria: Articles published in English Articles published on or after 2013 Articles that focused on human subjects Research on adult patients Exclusion criteria: Articles published in foreign languages Articles published prior to 2013 Research on animal models Articles on children and teenagers Level of evidences None of research papers were accessed easily and extracted following analysis of the titles and abstracts. (2014 ) Randomised controlled trial Database- MEDLINE Study design- Quantitative Research paradigm- Positivism No bias reported The study concluded that although proportion of

Bowel cancer
Name of the Student
Name of the University

PICO question
The PICO question for the research is given
below:
• Are chemotherapy drugs effective in
treating colorectal cancer?
• The key phrases and search terms used
for article extraction were “bowel
cancer”, “colorectal cancer”, “treatment”,
“fluorouracil”, “drug”, and
“management”. These key terms were
joined with the use of three boolean
operators namely, OR, AND, and NOT
(McGowan et al. 2016).
P Patients with
colorectal cancer
I Chemotherapy
drugs
C Usual care
O Reduced
symptoms

Selection criteria
• MEDLINE and CINAHL electronic databases were used for extracting articles relevant to the question
being investigated.
Inclusion criteria:
• Articles published in English
• Articles published on or after 2013
• Articles that focused on human subjects
• Research on adult patients
Exclusion criteria:
• Articles published in foreign languages
• Articles published prior to 2013
• Research on animal models
• Articles on children and teenagers

Level of evidences
• All research papers were accessed easily and extracted
following analysis of the titles and abstracts. Most articles
are of high quality evidences and have been appraised
with the use of the CASP toolResearch Number Research Type Source of database
1 Randomised Controlled
Trial
MEDLINE
2 Phase III CRYSTAL study MEDLINE
3 Randomised Controlled
Trial
MEDLINE
4 Randomised Controlled CINAHL

CASP tool
• The primary aim of using CASP was to develop a sense of the
research evidences, and applying them in practice.
• The CASP tool was utilised for adopting a structured approach that
would help in assessing the trustworthiness, value and rigour of the
articles (Singh 2013). The checklist was used for determining
whether the evidences presented in the articles can be used in
future practice.
• CASP tool for randomized controlled trial:
https://casp-uk.net/wp-content/uploads/2018/01/CASP-Randomised-C
ontrolled-Trial-Checklist-2018.pdf

Article 1- Heinemann et al. (2014)
• Randomised controlled trial
• Database- MEDLINE
• Study design- Quantitative
• Research paradigm- Positivism
• No bias reported
• The study concluded that although proportion of colorectal cancer patients
achieving objective responses did not meaningfully vary between
FOLFIRI+cetuximab and FOLFIRI+bevacizumab groups, the connotation with
lengthier complete survival proposed that FOLFIRI+cetuximab was the favoured
first-line regimen for all colorectal cancer patients, having KRAS exon 2 wild type
metastatic colorectal type of cancer.

Article 1- Heinemann et al.
(2014)
• Validity of research using CASP
• What were the findings? 184 patients present in the
FOLFIRI+cetuximab group were able to achieve objective response,
in comparison to 171 patients in the FOLFIRI+ bevacizumab group
• Are the results helpful? Yes
• Were the limitations addressed? No. This was the first randomised
controlled phase 3 trial that compared the efficacy of
FOLFIRI+cetuximab and FOLFIRI+bevacizumab in colorectal
cancer treatment

Article 2- Van Cutsem et al.
(2015)
• Post hoc investigation phase III CRYSTAL study
• Database: MEDLINE
• Study design- Quantitative
• Paradigm type- Not clear
• Probability of selection bias
• The researchers concluded that patients having RAS wild type tumours
were able to obtain significant benefits from administration of
cetuximab+FOLFIRI, while those having RAS tumor mutations failed to
report any benefits.

Article 2- Van Cutsem et al.
(2015)
• Validity of research using CASP
• What were the findings? Significant association found of
administration of cetuximab and FOLFIRI with KRAS exon 2
mutations among colorectal cancer patients
• Are the results helpful? Yes
• Were the limitations addressed? The analysis was restricted to
those patients of CRYSTAL study for whom an detectable DNA
tumour sample was available. There was lack of observed
advantages for patients with other mutations

Article 3- Tabernero et al. (2014)
• Randomised controlled trial
• Database- MEDLINE
• Study design- Quantitative
• Research paradigm- Positivism
• No bias reported
• The researchers concluded that profits of aflibercept, when administered
along with FOLFIRI among patients with metastatic colorectal cancer,
formerly treated with oxaliplatin were upheld across the subgroups, including
patients who were either subjected to prior bevacizumab treatment, or not.

Article 3- Tabernero et al. (2014)
• Validity of research using CASP
• What were the findings? Greater median overall survival were obtained
for FOLFIRI+aflibercept when compared to placebo (12.5 vs. 11.7) among
patients subjected to prior bevacizumab treatment; and 13.9 vs. 12.4 in
patients not subjected to the treatment.
• Are the results helpful? Yes.
• Were the limitations addressed? No. The authors suggested that
significant improvement was found in PFS and OS when aflibercept was
added to FOLFIRI for treatment of mCRC patients who were previously
treated with oxaliplatin.

Article 4- Cremolini et al. (2015)
• Multicentre, phase III randomised controlled trial
• Database- CINAHL
• Research Design- Quantitative
• Research paradigm type- Positivism
• No bias reported.
• The researchers identified FOLFOXIRI+bevacizumab as a practicable
treatment option for patients having bowel cancer, regardless of their
BRAF or RAS mutational status and baseline clinical characteristics.

Article 4- Cremolini et al. (2015)
• Validity of research using CASP
• What were the findings? The median overall survival was 29.8
months in the FOLFOXIRI+bevacizumab group (95% CI 26·0–34·3),
when compared to the FOLFIRI+bevacizumab group (25·8 months).
• Are the results helpful? Yes.
• Were the limitations addressed? No. The evidence presented by the
researchers strengthened the impact of FOLFOXIRI+bevacizumab
as a strategy for first-line treatment of people suffering from
metastatic bowel cancer.

Article 5- Stintzing et al. (2016)
• Multicentre, phase III randomised controlled trial
• Database- CINAHL
• Research Design- Quantitative
• Research paradigm type- Positivism
• No bias reported.
• The researchers were able to gain understanding about a new
framework that connected alternative response metrics to overall
rates of survival.

Article 5- Stintzing et al. (2016)
• Validity of research using CASP
• What were the findings? The median overall survival was greater
in FOLFIRI+cetuximab group, in comparison to
FOLFIRI+bevacizumab group (33·1 months [95% CI 24·5–
39·4] vs 25·0 months [23·0–28·1]).
• Are the results helpful? Yes
• Were the limitations addressed? No. FOLFIRI+cetuximab was
considered superior to FOLFIRI+bevacizumab in treatment of wild-
type metastatic bowel cancer.

Themes identified from evidences
• Administration of FOLFIRI, in combination with cetuximab
is an effective approach for the management of colorectal
cancer
• Administration of FOLFIRI, in combination with
bevacizumab is an effective approach for the management
of colorectal cancer
• FOLFIRI when administered to colorectal cancer patients,
in combination with aflibercept helps in the treatment.

Patient perspective
• The preferences and perspectives of the patients are often
difficult to measure, while conducting a randomised
controlled trial.
• There exists a lack of validated tools for assessing the
patient perspectives.
• Patient Reported Outcome Measures (PROMs) are
beneficial in assessing the quality of care that is delivered
to all NHS patients from their perspectives.

Patient perspective
• PROM currently cover four different clinical procedures, and
calculate the gain in health, following a treatment, with the use of
pre- and post-operative surveys (Kotronoulas et al. 2017).
• PROMs-driven needs assessments that are conducted by nurses,
among with patients with colorectal cancer have appeared acceptable
and feasible in clinical practice.
• They have been associated with a generous reduction in the incidence
of unmet requirements, and lesser reductions in psychosocial needs
and physical/daily living following the chemotherapy period.

Patient perspective
• EORTC QLQ-C30 has been identified as the commonly
used PROM among patients with bowel cancer (McNair et
al. 2015).
• Analysis of the surveys have helped in identification of 917
items, classified into 51 domains
• The domains comprise of fatigue, anxiety, and physical
function.

Clinician perspective
Chemotherapy drug Radiation therapy
Less invasive treatment method when
compared to other treatment procedures
Damage occurs to the surrounding tissues
Flexibility and patient convenience in location
and timing of administration (Neuss et al.
2013)
Fails to relieve mass effect
Drug exposure flexibility and less use of
healthcare resources
Results in increased wound complications like
poor wound healing

Complete evidence base
Evidence base
practice
Clinician perspectivePatient perspective

Limitations of study
• Small sample size
• Multiple medications might result in potential reactions among the patients
• The oral chemotherapy drugs might also interact with other prescribed
medications, herbal remedies, prescriptions, and OTC medications (if any)
(Segal et al. 2014).
• Nausea, odynophagia, dysphagia and vomiting might also present barriers
to administration or oral chemotherapy drugs
• Vomiting immediately after drug administration might reduce drug
absorption

Transforming evidence to practice
• Oral chemotherapy can be considered as a major part of the colorectal cancer
patient’s prescription drug plan.
• Upon administration, they will work in the bloodstream for damaging the rapidly
proliferating cancerous cells (Wong et al. 2014).
• Patients can be administered the drugs at schedules dosage at their home settings
• The dosage and administration will be monitored
• It will be enlisted as a pharmacy benefit
Evidence informed statement about best practice
• The drugs will not interfere with the patient lives
• This will provide them a greater sense of control

References
Cremolini, C., Loupakis, F., Antoniotti, C., Lupi, C., Sensi, E., Lonardi, S., Mezi, S., Tomasello, G., Ronzoni, M., Zaniboni, A. and Tonini, G., 2015. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab
as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. The Lancet Oncology, 16(13), pp.1306-
1315.
Heinemann, V., von Weikersthal, L.F., Decker, T., Kiani, A., Vehling-Kaiser, U., Al-Batran, S.E., Heintges, T., Lerchenmüller, C., Kahl, C., Seipelt, G. and Kullmann, F., 2014. FOLFIRI plus cetuximab versus
FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. The lancet oncology, 15(10), pp.1065-1075.
Kotronoulas, G., Papadopoulou, C., MacNicol, L., Simpson, M. and Maguire, R., 2017. Feasibility and acceptability of the use of patient-reported outcome measures (PROMs) in the delivery of nurse-led
supportive care to people with colorectal cancer. European Journal of Oncology Nursing, 29, pp.115-124.
McGowan, J., Sampson, M., Salzwedel, D.M., Cogo, E., Foerster, V. and Lefebvre, C., 2016. PRESS peer review of electronic search strategies: 2015 guideline statement. Journal of clinical epidemiology, 75,
pp.40-46.
McNair, A.G.K., Whistance, R.N., Forsythe, R.O., Rees, J., Jones, J.E., Pullyblank, A.M., Avery, K.N.L., Brookes, S.T., Thomas, M.G., Sylvester, P.A. and Russell, A., 2015. Synthesis and summary of patient‐reported
outcome measures to inform the development of a core outcome set in colorectal cancer surgery. Colorectal Disease, 17(11), pp.O217-O229.
Neuss, M.N., Polovich, M., McNiff, K., Esper, P., Gilmore, T.R., LeFebvre, K.B., Schulmeister, L. and Jacobson, J.O., 2013. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society
chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. Journal of Oncology Practice, 9(2S), pp.5s-13s.
Segal, E.M., Flood, M.R., Mancini, R.S., Whiteman, R.T., Friedt, G.A., Kramer, A.R. and Hofstetter, M.A., 2014. Oral chemotherapy food and drug interactions: a comprehensive review of the literature. Journal of
oncology practice, 10(4), pp.e255-e268.
Singh, J., 2013. Critical appraisal skills programme. Journal of Pharmacology and Pharmacotherapeutics, 4(1), p.76.
Stintzing, S., Modest, D.P., Rossius, L., Lerch, M.M., von Weikersthal, L.F., Decker, T., Kiani, A., Vehling-Kaiser, U., Al-Batran, S.E., Heintges, T. and Lerchenmüller, C., 2016. FOLFIRI plus cetuximab versus
FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. The Lancet
Oncology, 17(10), pp.1426-1434.
Tabernero, J., Van Cutsem, E., Lakomý, R., Prausová, J., Ruff, P., van Hazel, G.A., Moiseyenko, V.M., Ferry, D.R., McKendrick, J.J., Soussan-Lazard, K. and Chevalier, S., 2014. Aflibercept versus placebo in
combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. European journal of
cancer, 50(2), pp.320-331.
Van Cutsem, E., Lenz, H.J., Köhne, C.H., Heinemann, V., Tejpar, S., Melezínek, I., Beier, F., Stroh, C., Rougier, P., van Krieken, J.H. and Ciardiello, F., 2015. Fluorouracil, leucovorin, and irinotecan plus cetuximab
treatment and RAS mutations in colorectal cancer. Journal of clinical oncology, 33(7), pp.692-700.
Wong, S.F., Bounthavong, M., Nguyen, C., Bechtoldt, K. and Hernandez, E., 2014. Implementation and preliminary outcomes of a comprehensive oral chemotherapy management clinic. American Journal of
Health-System Pharmacy, 71(11), pp.960-965.

THANK YOU!