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 Table of Contents  
Year : 2022  |  Volume : 9  |  Issue : 3  |  Page : 400-405

Evaluation of chemotherapeutic regimen and associated adverse drug reactions of colorectal cancer in a tertiary care hospital

1 Department of Pharmacy Practice, St. Joseph’s College of Pharmacy, Cherthala, India
2 Department of Oncology, Lourdes Hospital, Post Graduate Institute of Medical Science & Research, Kochi, Kerala, India

Date of Submission18-Jul-2022
Date of Acceptance05-Sep-2022
Date of Web Publication29-Sep-2022

Correspondence Address:
Mrs. R Lakshmi
Department of Pharmacy Practice, St. Joseph’s College of Pharmacy, Cherthala 688524, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mgmj.mgmj_112_22

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Background: Colorectal cancer (CRC) is the fourth most common cause of death diagnosed in both men and women. Though there are modifiable and non-modifiable risk factors for CRC. cancer patients encounter chemotherapy-associated drug interactions and adverse drug reactions hence the need for such a study will help the professionals to improve the patient’s quality of life. Materials and Methods: A six-month retrospective study of 130 patients who satisfied the inclusion and exclusion criteria was conducted by collecting data from November 2020 to May 2021. Data was collected from the Mediware system of the hospital using specially designed data collection forms. Results: Out of 130 patients, 61.51% were male and most of the patients were more than 60 years old. In this study, 11 patients had a history of smoking and alcoholism and 4% had a family history of CRC. Comorbidities associated with CRC were HTN and DM. In the study, stage 4 cancer patients were found to be more. 77.69% of patients had received chemotherapy along with surgery, and the most commonly prescribed regimen was Capcetabine and OxaliplatinThe length of hospital stay was increased for the FOLFOX (Oxaliplatin, 5-Fluorouracil, and Leucovorin) regimen. The common ADR analyzed was constipation, followed by vomiting and neutropenia, and most ADRs were associated with the CAPOX regimen (diarrhea) and treated accordingly.10 patients had febrile neutropenia, 5 patients had grade 4 neutropenia and all were treated with antibiotics and filgrastim. Febrile neutropenia was seen in patients with metastasis. Conclusion: Timely and appropriate treatment for ADRs and early screening can improve the quality of life of individuals. Further studies on this topic will help to improve the treatment quality provided by professionals

Keywords: Adverse drug reactions, chemotherapeutic regimen, colorectal cancer, febrile neutropenia, risk factors

How to cite this article:
Mol LS, Jose A, Mohan A, Madhu C S, Lakshmi R. Evaluation of chemotherapeutic regimen and associated adverse drug reactions of colorectal cancer in a tertiary care hospital. MGM J Med Sci 2022;9:400-5

How to cite this URL:
Mol LS, Jose A, Mohan A, Madhu C S, Lakshmi R. Evaluation of chemotherapeutic regimen and associated adverse drug reactions of colorectal cancer in a tertiary care hospital. MGM J Med Sci [serial online] 2022 [cited 2023 Feb 6];9:400-5. Available from: http://www.mgmjms.com/text.asp?2022/9/3/400/357483

  Introduction Top

Colorectal cancer is among the top 5 cancers and the third most common malignancy in men and women.[1] Modifiable and non-modifiable risk factors along with family history contribute to Colorectal cancer (CRC). Treatment consists of surgery, radiation therapy, chemotherapy, and biomodulators. Commonly, regimens like FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin), FOLFOX(Oxaliplatin, 5-Fluorouracil, and Leucovorin), FOLFOXIRI regimen (combination of Irinotecan, Oxaliplatin, Fluorouracil, and Leucovorin), CAPOX regimen(Capcetabine and Oxaliplatin) CAPIRI (Capcetabine and Irinotecan) and XELIRI regimen (combination of Capecitabine and Irinotecan) are used.[2]Chemotherapy-related ADR can reduce a patient’s quality of life, and prolong hospitalization hence increasing expenses. ADRs associated with chemotherapy are neutropenia, febrile neutropenia, gastrointestinal, Neuro, cutaneous, and cardiovascular toxicity with hypersensitivity, alopecia, and constipation.[3],[4] Febrile neutropenia is neutropenia (≤1.5 × 109/l) accompanied by a temperature of ≥ 38.3°C following chemotherapy or hospitalization for fever infection.[5],[6] Management of ADRs involves treatment using antibiotics, antifungals, antiemetics, electrolytes, probiotics, filgrastim, vitamins, and analgesics. The dilemma mostly faced by the patients on chemotherapy is adverse drug reactions(ADRs). Through this study, timely and appropriate treatment for ADRs as well as ample monitoring and early screening can be done by pharmacists and other professionals to improve the quality of treatment thereby the quality of life of the patient and can lead to the development of other molecules for therapy.

  Materials and methods Top


A six months retrospective single-center study was conducted by taking data from November 2020 to May 2021 after obtaining the approval of the hospital ethical committee for 130 patients. The study was carried out in the department of oncology, Lourdes hospital, Kochi, Kerala, India. Patients were selected based on a convenient sampling method from the oncology department comprising inpatients and outpatients who satisfied the inclusion and exclusion criteria.

Inclusion criteria

  • ➢ All patients diagnosed with colorectal cancer on chemotherapeutic management.

  • ➢ Patients above 18 years of age.

Exclusion criteria

  • ➢ Patients with incomplete data.

The data were collected using a specially designed data collection form. The patient’s laboratory, as well as treatment details, were extracted from the medical records and Mediware system. Based on inclusion and exclusion criteria inpatient and outpatient case files were randomly selected and reviewed and assessed. Details of individual cases required to answer the objectives were entered into a predesigned data collection form. The patient details such as demographic details, treatment history, home medications, adverse drug reactions, etc were recorded in data collection form for review and assessment. Analytical techniques were performed using SPSS software for the assessment of data. Analyses were carried out at a 5% level of statistical significance. During reference, Up-to-date software was used as a reference for analyzing chemotherapeutic regimens and adverse drug reactions of different chemotherapeutic agents.

  Results Top

A total of 328 colorectal cancer cases were collected and analyzed which included cases of surgery, chemotherapy, and radiation.130 patients who met the eligibility criteria were selected for the study.

Risk factors associated with Colorectal cancer in the study population

Non-modifiable risk factors for CRC include age, race, colorectal polyps, gastrointestinal disorders, genetic cancer syndromes, family history, and other cancers. Modifiable risk factors such as smoking, alcohol, obesity, lack of physical activity, increased consumption of processed foods and red meat, and decreased fruit and vegetable consumption in the daily diet all increase the likelihood of CRC such as previous cancers, cardiovascular disease, hypertension and side effects of medical procedures also contribute to the incidence of CRC.[2]

The majority of the individuals (49.23%) having CRC were in the age group of greater than 60 years of which 13.84% were females and 35.38% were males. The mean age was found to be 59 ± 11.5772. The minimum and maximum ages in our study population were 21 and 89 years respectively. Among the study population, 54.6% had normal BMI, 8.46% of patients were having a positive history of smoking and alcoholism, and 4% of patients had a positive family history of cancer. HTN (30%) and DM (29.23%) were the most common comorbidities seen in the study population.

Metastasis and sites

On investigation, it was found that the majority of patients were having metastasis 69 [53.07%], among them, 8.69% had multiple site metastasis (lung and liver 3 cases, lung and bone 1 case, lung and brain 1 case sacrum and liver 1 case). Out of 69 patients with metastasis, the most common site of metastasis was found to be the liver (23.18%). Results show that rectal cancer patients were most likely present with lung only (3 patients) and liver-only metastasis (9 patients) and colon cancer patients were having more liver-only metastasis (7 patients).

Treatment, staging, duration of hospitalization

FOLFIRI regimen (Irinotecan, 5-Fluorouracil and Leucovorin), FOLFOX regimen (Oxaliplatin, 5-Fluorouracil and Leucovorin), FOLFOXIRI regimen (combination of Irinotecan, Oxaliplatin, Fluorouracil and Leucovorin) and XELIRI regimen (combination of Capecitabine and Irinotecan).[2]

Different treatments were received by the study population in which most of the patients received chemotherapy along with surgery 101 (77.69%). Other treatments include chemotherapy with surgery and radiation 19 (14.61%), 7(5.38%) of them had chemotherapy alone and 3 (2.30%) of them had chemotherapy with radiation. Major chemo regimens received by patients were CAPOX [60%]as shown in[Table 1]]. On assessing the duration of hospitalization, 1–7 days of hospitalization was seen in [80%] study population. The population who used the CAPOX regimen showed a hospitalization of greater than 14 days. There was an association between the FOLFOX regimen and length of hospital stay (p-value <0.05). Colorectal cancer was staged into 4 categories from stage 1 to 4 and the results reflected was 21.5% had stage 3 and 18.5% had stage 4, 10% patients had stage 2, and 3.1% patients had stage 1 CRC as illustrated in [Table 2].
Table 1: Chemotherapy regimens received by the study population

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Table 2: Length of hospital stay and Stage of cancer in the study population

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Outcome of treatment

Patients were divided and analyzed based on the outcome by categorizing them into favorable cases which mainly include cases that come under lesser days of hospital stay, the lower stage of cancer, and unfavorable vice versa. Treatment outcome was studied to find a suitable treatment regimen. The duration of hospitalization of 12.30% of patients was prolonged and 6.15% of patients died. Among the patients in the age group >60 years, 6 [4.61%] had unfavorable outcomes (prolonged hospital stay). Overall, 95.4% (124) of patients had a favorable outcome. Among female patients, 57.69% had a favorable outcome and 3.84% had an unfavorable outcome. In male patients, 37.69% had a favorable outcome and 0.76% had an unfavorable outcome. Though the number of females is lesser than males in our study it is evident that females showed comparatively more favorable outcomes than males as given in [Table 3].
Table 3: Treatment outcome based on age and gender of the study population

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ADRs reported in the study population

The main ADRs associated with chemotherapy are neutropenia and febrile neutropenia. Other toxicities associated with them are gastrointestinal toxicity [nausea, vomiting, diarrhea, and mucositis], Neurotoxicity [peripheral neuropathy], Myelosuppression (anemia, thrombocytopenia, neutropenia), cutaneous or integument toxicity (follicular rash, Hand-Foot Syndrome), Cardiovascular toxicity, hypersensitivity, alopecia, constipation, fatigue, black or bloody rectum stool, bruising and bowel habit changes.[3],[4]

79 patients were having ADRs, among them constipation [20.56%] was the most common ADR followed by vomiting (19.85%) and neutropenia (19.1%). Among the 79 patients with ADR, 20% had only one ADR and 30.76% had more than two ADRs. After studying the overall ADR occurrence, individual regimens and the occurrence of respective ADRs were studied. In FOLFOX regimen occurrence of neutropenia was 28.6%, constipation (35.7%), diarrhea (7.1%), vomiting (21.4%) while in FOLFIRI regimen neutropenia (15.4%), constipation (15.4%), vomiting (15.4%) and diarrhea (7.7%). There was a positive association between CAPIRI regimen and diarrhea with a p-value less than <0.001 [OD 14.533, 95%CI 2.448–86.278]. There was an increased incidence of diarrhea with capecitabine [OD 12.941, 95%CI 1.112- 150.597], nausea [OD 20.667 95% CI 1.446–295.349], and diarrhea [OD 0.849, 95% CI 0.789–0.914] with FOLFOX and bevazizumab regimen as depicted in [Figure 1].
Figure 1: ADRs reported in the study population

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Febrile neutropenia, categorization, management

10 [7.69%] patients had Febrile Neutropenia. Incidence of FN was mostly associated with FOLFIRI + cetuximab regimen [OD 29.750, 95% CI 2.430–364.2], CAPOX + bevazizumab [OD 0.922, 95%CI 0.877–0.970] and capcetabine [OD 0.921, 95% CI 0.876–0.969]. There was a positive association between CAPIRI regimen and FN with a p-value less than 0.001. There is a positive association between FN and anemia with a p-value less than 0.05 (P = 0.033) and also with metastasis having a p-value less than 0.05 (P = 0.015) [OD 95% CI, 1.106–73.257]. Out of 10 febrile neutropenia patients, 5 (50%) patients had grade 4 neutropenia. Antibiotics were prescribed for 8 patients (80%), filgrastim was prescribed for 3 (30%) patients, paracetamol was prescribed for 2 patients (20%) and 4 patients (40%) were under a neutropenic diet. Grade 4 patients were treated with inj. filgrastim, candid mouth paint. Grade 3 patients treated with cefixime ofloxacin combination, Inj. filgrastim. Grade 1 was treated with inj. filgrastim and antibiotics. Apart from this most patients were following a neutropenic diet and for fever, paracetamol was given.

  Discussion Top

Siegel et al. in their study conducted in 2020 state that the lifetime risk of CRC is similar in men (4.4%) and women (4.1%) the incidence rate is 31% higher in men. Incidence is comparable in those younger than 45 years, but it is 40% to 50% higher in men than in women aged 55 to 74 years.[2] In our study also similar results were observed with an approximately equal incidence in both males and females under the age of 60 years, whereas a greater number of cases is reported in male patients of age greater than 60 years. 83.8% (109) patients of age >50yrs have an incidence of colorectal cancer and 16.2% (21) patients of age <50 yrs.

Siegel et al. conducted a study in the year 2020, states that approximately 147,950 individuals were diagnosed with CRC and 53,200 individuals died from the disease, including 17,930 cases and 3,640 deaths in individuals aged younger than 50 years, which is similar to our study stating that a greater number of patients are alive due to treatment and percentage of death is less.[2]

Fay Kastrinos conducted a study in 2019 stating families with a history of CRC carry genetic variants that cause CRC with high or moderate penetrance, but these account for only 5% to 10% of CRC cases which is similar to our study showing less than 5% cases with CRC history.[7]

Fowler H, et al. conducted a study to estimate the prevalence of comorbid conditions among cancer patients. And reported that 15–20% had HTN and 5% of patients had DM. In their study, HTN is about 55.7% and DM is about 54.28%.[8] In our study, the most reported comorbidity was HTN, which was similar to their study. White A, et al. conducted a study to identify sex-related differences in CRC incidence, screening, diagnosis, staging, and survival in the UK. From this study, the proportion of CRC cases in the rectum and sigmoid colon are higher in males than females.[9] In our study, CRC is most common in males (80) than in females (50), which was similar to their study. Robinson JR et al. conducted a study among 1,202 individuals, and compared liver metastasis in colon and rectal cancers and their results show that compared to patients with proximal colon primaries, patients with rectal primaries were more likely to present with lungs-only or liver and lungs metastases versus liver-only metastases.[10] These results were similar to our study, showing that 16 patients had liver metastasis.

A study was conducted by Chalya PL, et al. to describe the clinicopathological pattern of CRC and to highlight the challenging problem in the management of CRC. Out of 332 patients, 326 patients underwent surgical procedures and 54 out of 321 patients received adjuvant treatment.[11] In our study, 101 patients were managed with both chemotherapy and surgery. Only 7 patients were managed with chemotherapy alone. Saeedeh pourahmad et al. conducted a study to determine the CRC stage using 3 methods based on preoperative clinical findings. Out of 117 patients 17.1% in stage 1, 33.3% in stage 2, 44.4% in stage 3 and 5.2% in stage 4. In this study, most of the patients come under stage 3(44.4%) which is similar to our study.[12]

Andre T, et al. conducted a study on 1123 patients. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatments for colon cancer.[13] Out of 237 colon cancer patients treated with Fluorouracil, Leucovorin + Oxaliplatin, the incidence of febrile neutropenia was 1.8%, and the incidence of gastrointestinal adverse effects was low. But according to our study out of 12 colon cancer patients treated with FOLFOX, 2 patients had febrile neutropenia (16.66%). The incidence of GI adverse effects was high (66.66%). The results were found to be different from our study.

Negarandeh R, et al. conducted a study “Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives” in 88 patients. In a comparison of FOLFOX and FOLFIRI regimens, there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting, and oral mucositis.[14] In our study also comparing the two regimens there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting, and oral mucositis. In CAPIRI regimen occurrence of diarrhea was 66.7% and neutropenia was 33.3%, anemia, mucositis, and abdominal pain were 16.7%, whereas in CAPOX neutropenia was 16.5%, vomiting was 24.1% and constipation was 24.1%.

Kim D, et al. conducted a study on cancer patients, Incidence, and Clinical Outcomes of Febrile Neutropenia in Adult Cancer Patients with Chemotherapy Using the Korean Nationwide Health Insurance Database.[15] The results were similar to our study. The incidence of FN was 9.5% in CRC patients. In our study, the incidence of febrile neutropenia in CRC patients was similar (7.69%).

  Conclusion Top

This study notifies the influence of risk factors and comorbidities mainly age (>50 years), gender (male), alcoholism, and smoking on colorectal cancer. The dilemma mostly faced by the patients on chemotherapy is adverse drug reactions. Incidence of Grade 4 febrile neutropenia along with others like constipation and vomiting were noted in most cases and mostly with CAPIRI regimen. A favorable outcome is observed among the female population and also from the study it is evident that staging plays a key role in the length of hospital stay. further studies on this topic will be useful for the development of new molecules and also quality of life can be improved.

Ethical consideration

The Institutional Ethics Committee, Lourdes Hospital, Postgraduate Institute of Medical Science and Research, Kochi, Kerala, India has approved the study protocol vide their letter no. LH/EC/2020–42 dated 26.11.2020.


Due to the pandemic episode of COVID-19 and the retrospective nature of the study the data collection was limited.

Follow-up of some patients was lost due to some unforeseen reasons.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There is no conflict of interest.

  References Top

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.  Back to cited text no. 1
Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin 2020;70:145-64.  Back to cited text no. 2
Grenon NN, Chan J Managing toxicities associated with colorectal cancer chemotherapy and targeted therapy: A new guide for nurses. Clin J Oncol Nurs 2009;13:285-96.  Back to cited text no. 3
Kishore P, Meghana G, Reddy BP, Raghavaiah KV The pattern of adverse drug reactions and its management in female cancer patients in a private hospital in Telangana, India. Asian J Pharm Res Dev 2018;6:45-53.  Back to cited text no. 4
Hosmer W, Malin J, Wong M Development and validation of a prediction model for the risk of developing febrile neutropenia in the first cycle of chemotherapy among elderly patients with breast, lung, colorectal, and prostate cancer. Support Care Cancer 2011;19:333-41.  Back to cited text no. 5
Rasmy A, Amal A, Fotih S, Selwi W Febrile neutropenia in cancer patient: Epidemiology, microbiology, pathophysiology, and management. J Cancer Prev Curr Res 2016;5:00165. doi: 10.15406/jcpcr.2016.05.00165.  Back to cited text no. 6
Kastrinos F, Samadder NJ, Burt RW Use of family history and genetic testing to determine risk of colorectal cancer. Gastroenterol 2020;158:389-403.  Back to cited text no. 7
Fowler H, Belot A, Ellis L, Maringe C, Luque-Fernandez MA, Njagi EN, et al. Comorbidity prevalence among cancer patients: A population-based cohort study of four cancers. BMC Cancer 2020;20:2.  Back to cited text no. 8
White A, Ironmonger L, Steele RJC, Ormiston-Smith N, Crawford C, Seims A A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK. BMC Cancer 2018;18:906.  Back to cited text no. 9
Robinson JR, Newcomb PA, Hardikar S, Cohen SA, Phipps AI Stage IV colorectal cancer primary site and patterns of distant metastasis. Cancer Epidemiol 2017;48:92-5.  Back to cited text no. 10
Chalya PL, McHembe MD, Mabula JB, Rambau PF, Jaka H, Koy M, et al. Clinicopathological patterns and challenges of management of colorectal cancer in a resource-limited setting: A tanzanian experience. World J Surg Oncol 2013;11:88.  Back to cited text no. 11
Pourahmad S, Pourhashemi S, Mohammadianpanah M Colorectal cancer staging using three clustering methods based on preoperative clinical findings. Asian Pac J Cancer Prev 2016;17:823-7.  Back to cited text no. 12
André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343-51.  Back to cited text no. 13
Negarandeh R, Salehifar E, Saghafi F, Jalali H, Janbabaei G, Abdhaghighi MJ, et al. Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients. BMC Cancer 2020;20:560.  Back to cited text no. 14
Kim D, Lee S, Youk T, Hong S Incidence and clinical outcomes of febrile neutropenia in adult cancer patients with chemotherapy using korean nationwide health insurance database. Yonsei Med J 2021;62:479-86.  Back to cited text no. 15


  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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