|Year : 2021 | Volume
| Issue : 2 | Page : 530-536
A prospective observational study of chemotherapy-induced adverse drug reaction and the quality of life in cancer patients in a tertiary care hospital
D Krishnarajan, K Sivasakthi, R Ariyamol, D Naveen Kumar, Soniya Varghese
Department of Pharmacy Practice, JKK Munirajah Medical Research Foundation, College of Pharmacy, The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India
|Date of Submission||22-Nov-2019|
|Date of Decision||23-May-2020|
|Date of Acceptance||16-Jul-2020|
|Date of Web Publication||11-Jun-2021|
D Naveen Kumar
98, West Street, Nainarpalayam, Kallakurichi, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aim: The aim was to study the pattern of adverse drug reaction (ADR) provoked by anticancer therapy and to assess the quality of life (QoL) in cancer patients.
Materials and Methods: This study was conducted in Tamil Nadu on 75 patients from February to July 2019 taking into account their demographic profile, ADR occurrence and its causality, outcome, organ system-wise distribution of ADRs, and others. The causality assessment was done by using Naranjo's scale and QoL was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale. The QoL was compared in any two consecutive cycles between the 2nd and 5th cycles of chemotherapy.
Results: Out of the 75 patients, 17 male and 56 female patients developed ADR. A total of 228 ADRs were observed in 73 patients. The most commonly occurred ADR was nausea and vomiting (45%) and the most commonly affected system was gastrointestinal tract (37%). According to causality assessment, the ADR that occurred falls mostly in the category of probable (66.7%) followed by possible (29.3%) and the outcome of the ADR was mostly recovering (49.3%). The QoL was higher in females and in the age group of 40–49 years. The physical and emotional well-being of the patient were affected more. The overall QoL was improved in the 2nd visit when compared to the 1st visit.
Conclusion: Cancer is known to cause a significant impact on the health and socioeconomics of a nation. To boost the QoL in patients, it is essential to identify and manage the ADRs by taking appropriate measures to promote judicious use of drugs.
Keywords: ADR, cancer, chemotherapy, Functional Assessment of Cancer Therapy-General, Naranjo scale, quality of life
|How to cite this article:|
Krishnarajan D, Sivasakthi K, Ariyamol R, Kumar D N, Varghese S. A prospective observational study of chemotherapy-induced adverse drug reaction and the quality of life in cancer patients in a tertiary care hospital. J Can Res Ther 2021;17:530-6
|How to cite this URL:|
Krishnarajan D, Sivasakthi K, Ariyamol R, Kumar D N, Varghese S. A prospective observational study of chemotherapy-induced adverse drug reaction and the quality of life in cancer patients in a tertiary care hospital. J Can Res Ther [serial online] 2021 [cited 2021 Sep 23];17:530-6. Available from: https://www.cancerjournal.net/text.asp?2021/17/2/530/318104
| > Introduction|| |
Cancer burden in India has more than doubled over the last 26 years, as it is the highest among all the therapy areas. Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, resulting in 6.5%–10.9% of hospital admissions and mortality rates of 0.15%–2.9%, and are a source of additional economic burden to the patients, their caregivers, and the health-care systems that treat them. A clinical pharmacist plays an important role in the early detection of these ADRs, which may help in minimizing the damage by treating and preventing the ADRs and by either modifying the dose or changing the offending agent.,
In India, cancer can have profound social and economic consequences on people, often leading to family impoverishment and societal inequity. Quality of life (QoL) has become a well-accepted outcome measure for cancer patients and an integral part of cancer patient management.,, Although patients' QoL decreases when receiving cancer chemotherapy, it is desirable that pharmacists support the treatment providing guidance, listening to patients who have undergone chemotherapy, and collaborating with other professionals to maintain and improve patients' QoL. The present study aims to identify and characterize the pattern of ADRs induced by chemotherapeutic agents and assess the QoL for them.
| > Subjects and Methods|| |
The present study was a prospective, observational study conducted in a tertiary care hospital in the oncology department, Salem, Tamil Nadu, for 6 months. After obtaining approval from the Institutional Ethics Committee (Reference number EC/PHARM D/2019.04), the study was started in the universal hospital, Salem, Tamil Nadu. At first, 84 patients were included in the study after obtaining the informed consent from the patients, but only 75 patients were enrolled in the study finally. The remaining nine patients were neglected because they do not have a proper follow-up for the next cycle of chemotherapy due to economic burden, other personal issues (illness, went to some other hospital, or not continuing therapy), and insufficient data. The inclusion criteria of the study were patients in the age group of 18 and above, patients who receive chemotherapy between the 2nd cycle and 5th cycle, patients who undergo both radiation therapy and surgery, and patients with all types of cancer. Patients who are not willing to participate in the study and unable to respond were excluded from the study.
A separate data entry form was prepared to record patient demographic details, type of cancer affected, number of chemotherapy cycles completed, type of chemotherapy drugs taken, suspected ADR occurrence, and category and outcome of ADR. To assess the causality of chemotherapy-induced ADR, the Naranjo ADR Probability Scale was used. The Naranjo ADR Probability Scale consists of ten questions that are answered as either Yes, No, or “Do not know.” Different point values (−1, 0, +1, or +2) are assigned to each answer. The total score ranges from −4 to +13; the causality of ADR is considered definite if the score is 9 or higher, probable if 5–8, possible if 1–4, and doubtful if 0 or less. The outcome of the ADR was recorded under six categories as fatal, continuing, recovering, recovered, unknown, and others.
The Functional Assessment of Cancer Therapy - General (FACT-G Scale [Version 4.0]) was used to measure QoL in cancer patients receiving therapy. It comprises the core set of questions, which can be answered by a broad range of patients. It consists of four subscales: physical well-being (PWB; score range 0–28), emotional well-being (EWB; 6 items, score range 0–24), social/family well-being (SWB; 7 items, score range 0–28), and functional well-being (FWB; 7 items, score range 0–28). All questions in the FACT-G use a 5-point Likert scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; and 4 = very much). Circling or marking one number per question is used to indicate the response of the patient as it applies to the past 7 days. The total score ranges from 0 to 108. The higher score indicates the patient's higher QoL. The QoL was compared in any two consecutive cycles between the 2nd and 5th cycles of chemotherapy. The FACT-G scale applies to the past 7 days, so this study measures QoL from the 2nd chemo cycle onward. Measuring QoL was limited up to the 5th cycle because some patients would have completed their chemotherapy cycles within that period. The duration/gap between the two chemotherapy cycles may vary depending on the type of drugs used and type and severity of cancer. Most of the chemotherapy regimens in this study were given as weekly chemotherapy cycle (7 days once). However, 14-day or 28-day chemotherapy cycles were also given in some cases, depending on the type of drug regimen and cancer type.
It is a 3-point contact with the study participants. At first, patients' demographic details in a separate data entry form were filled. During the first review, the patients were assessed for causality & outcome of the ADRs induced by anticancer drugs and then the QoL among these patients were assessed by interview the Fact-G Questionnaire for past 7 days response of the priorly given chemotherapy. At the 2nd review, the patients were re-assessed with the same questionnaires of QoL. The difference between FACT-G scores of the two reviews indicates the increase or decrease in QoL due to chemotherapy for each patient.
Statistical procedures were performed by using Microsoft Office Excel Worksheet and GraphPad InStat Version 3.1. (GraphPad software company, San Diego, California, U.S). The interpretations were performed for the continuous variables by mean difference and Student's t-test and using the χ2 test for categorical variables. P ≤ 0.05 was fixed as the level of statistical significance.
| > Results|| |
In this study, 75 patients were enrolled and among them, 73 patients experienced 228 ADRs and the remaining two patients have not developed any specific ADR. The demographic details are summarized in [Figure 1]. The prevalence of cancer was higher in females (77.3%) than males (22.7%), and the incidence/rate of ADR occurrence was higher in males in our study population. The patients in the age group of 50–59 years were more affected by ADR occurrence. The rate of ADR occurrence was higher in metastatic patients (3.3) when compared to nonmetastatic patients (2.9) in our study. This states that metastatic cancer patients are more prone to the occurrence of ADR. Hence, health-care professionals like physicians or clinical pharmacists should focus more in the area of suspected ADR for metastatic cancer patients belonging to the age group of below 50–59 years.
|Figure 1: Demographic overview of age, gender, and category with the occurrence of adverse drug reactions|
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[Figure 2] shows 17 types of cancers observed in our study. Out of these, the most prevalent type of cancer was breast cancer diagnosed in 22 patients (29.3%) followed by cervical cancer in 20 patients (26.7%); lung cancer in seven patients (9.3%); ovarian cancer in six patients (8%); and each of pancreas, neck, urothelial, cecum, uterus, penis, colon, brain, and rectal cancer in one patient (1.3%).
In this study, 228 ADRs of 29 types were observed in 73 patients. Among these, nausea and vomiting was the most common ADR seen in 34 patients (45%), followed by fatigue in 31 patients (41%), alopecia in 25 patients (33%), and anemia in 20 patients (27%).
[Figure 3] describes the eight types of organ system affected due to chemotherapy-induced ADR. Among them, the majorly affected system was gastrointestinal tract (36.4%) followed by muscular system (22.4%), dermal (17.1%), hematology (9.6%), and nervous system (7.5%).
|Figure 3: Categorization of system affected due to adverse drug reaction|
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[Figure 4] shows 22 types of chemotherapy drugs which were administered (as singlet-/doublet-/triplet-drug therapy) to various types of cancer patients depending on the patient condition, cancer type, disease stage, and drug tolerance. Cisplatin was the most common drug prescribed in our study as it was the single-agent therapy. It is the predominant drug in our study. Carboplatin + paclitaxel and doxorubicin + cyclophosphamide were the combination agents prescribed commonly. In this study, patients were treated with nearly an equal amount of single- (36 patients) and combination-drug therapy (39 patients). The number of ADRs occurred due to both single-drug therapy (110 ADRs) and combination-drug therapy (118 ADRs) was nearly equal, which occurred based on the number of patients treated.
|Figure 4: Incidence of adverse drug reaction in different types of chemotherapy prescribed|
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[Figure 5] depicts the causality of ADR and its outcome. According to Naranjo's algorithm, most of the ADRs probably occurred (66.7%) followed by possible (29.3%), definite (1.3%), and two patients had no ADR, which was categorized as doubtful (who had a Naranjo scale score of 0). Most of the ADRs were in recovering phase in 36 patients (51.8%) followed by continuing (31.1%), recovered (16.7%), and no fatal/unknown ADRs.
|Figure 5: Evaluation of causality and outcome of the adverse drug reactions|
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In the FACT-G scale, high score indicates higher QoL. The QoL had improved in both males and females. However, the QoL and its rate of improvement were higher in females when compared to males [Figure 6]. The rate of ADR occurrence was lower in females as shown in Figure 1. ADR occurrence was inversely proportional to the QoL.
The QoL had highly improved in the age group of 40–49 years. The negative mean difference indicates decreasing QOL. The QoL in the age groups of 18–29 and 29–39 had decreased (with mean differences of −8.4 and −7.3, respectively) because one patient in each group had metastatic cancer and their education and regular job were affected severely [Figure 7].
The QoL was high in patients who received chemotherapy only (78.2–83.1). However, the QoL had improved greatly in patients who had undergone treatment of chemotherapy + radiotherapy + surgery (mean difference of 5.1) by comparing visit 1 and visit 2, which is depicted in [Figure 8].
In this study, QoL was higher in patients who received chemotherapy of docetaxel + cisplatin + 5-flurouracil (98–94) and QoL had improved highly in patients who received chemotherapy of cisplatin + paclitaxel (60.3–80.1). This reveals that the QoL was greater for the combinational chemotherapy than single-agent chemotherapy regimen. Temozolomide chemotherapy affected the QoL more [Figure 9]. Various factors such as prescribing pattern, drug tolerance, and patient specificity may influence the above results if the same drugs were given in different regions on different population.
|Figure 9: Comparison of quality of life in different chemotherapy drugs prescribed|
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The QoL in two patients without ADR (87.6–95.8) was greater. The QoL had improved highly in patients who were treated for ADRs (75.4–80.2) when compared to ADR-untreated patients (71.0–73.5), which is depicted in [Figure 10].
The QoL and its rate of improvement were greater in nonmetastatic cancer patients (75.9–79.6) than metastatic patients (70.5–73.5), as shown in [Figure 11].
|Figure 11: Comparison of quality of life in metastatic and nonmetastatic cancer patients|
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As shown in [Figure 12], the comparison of FACT-G subscale scores shows that cancer patients were highly affected in the domain of PWB (such as lack of energy, nausea, pain, and forced to spend time in bed) and EWB (such as losing hope in fight against illness, feeling sad, and worrying about if condition may worse) due to the cancer disease, drug therapy, ADR occurrence, and other factors.
|Figure 12: Evaluation of quality of life over the Functional Assessment of Cancer Therapy-General subscales|
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Most of the patients had their QoL with a mean FACT-G score of 60–80, which is above the average level. Their overall QoL improved with the mean difference of 3.5 (3.2%) while comparing the 1st and 2nd assessments, as shown in [Figure 13].
|Figure 13: Overall comparison of quality of life in the 1st and 2nd visits|
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| > Discussion|| |
This study reveals that the prevalence of cancer is higher in females (77.3%) than males (22.7%), which is similar to the study of Vinodkumar et al., Kumar et al., Sharma et al., and other studies.,,,, This indicates that females were majorly affected due to cancer when comparing males. The incidence/rate of ADR occurrence was higher in males, which is also similar to the study of Vinodkumar et al. The ADR was highly observed in the age group of 50–59 years, which is similar to the study conducted by Sharma et al. and Prasad et al.,
In the present study, the most common type of cancer was breast cancer followed by cervix, lung, and ovary. This is similar to the findings of Sunny et al., which reveal breast cancer (22%) as the most common type of cancer, followed by stomach, lung, and ovary., Another study by Shrestha et al. found lung cancer to be the common type followed by ovary, breast, stomach, and cervical cancers, which is contrary to our study.
Among the 22 types of chemotherapy administered, carboplatin + paclitaxel and doxorubicin + cyclophosphamide were the combination agents prescribed commonly, which is similar to the findings of Sunny et al. Monotherapy with cisplatin (23 patients) was more commonly prescribed followed by docetaxel, paclitaxel, and gemicitabine, which is contrast to the study conducted by Vinodkumar et al.,
Nausea and vomiting was found to be the most common ADR in our study, which is similar to the studies conducted by Kumar et al. and Keshri et al.,,, This could be due to the fact that chemotherapy-induced nausea and vomiting could have been caused by activation of chemoreceptor trigger zone. Although vomiting is a common problem associated with cancer chemotherapy, prevential therapy/measures need to be taken by the prescriber. The most commonly affected system was gastrointestinal tract (36.4%), which is similar to the findings of Chopra et al. and Keshri et al.,
According to Naranjo's algorithm, around 66.7% of adverse drug reactions were probable in causality, 29.3% were possible, and 1.3% were definite. Similar findings were reported in few studies conducted by Prasad et al., Vinodkumar et al., and Shrestha et al.,, A study done by Chopra et al. was reported as causality of ADRs were majorly possible followed by probable which was contrary to our study.
Shrestha et al. reported that 44.3% of ADRs were completely recovered, whereas 24.6% were recovering, 19.7% ADRs were still continuing, 9.8% were unknown, and 1.6% were fatal. It is contrary to our study which reported that 51.8% of ADRs were recovering followed by 31.1% of ADR being continuing, 16.7% being recovered, and there were no fatal/unknown ADRs.
A study by Holzner et al. reported that the mean values of FACT-G subscales usually declined with increasing age, which is moreover similar to our study, but while comparing the rate of improvement of mean QOL values in the 2nd visit, it was contrary to our results above.
To the best of our knowledge, this is the first study from South India which assessed both ADR and QoL in cancer patients and derived a relationship between them. In general, chemotherapy may induce various types of ADR to the cancer patients, so there is a suspicion that whether chemotherapy may increase or decrease the QoL. Even though chemotherapy induces ADR, our study reveals that “QoL was improved in the 2nd review of the patients by chemotherapy.” This could be due to the illness of cancer (pain and other signs), which decreased day by day in most of the patients and ADRs were monitored, detected, and treated. This study also reveals that the QoL in patients without ADR was higher and QoL was improved in patients who were treated for ADRs when compared to those with untreated ADR. This study provides the baseline data regarding the distribution of ADR and QoL in various categories such as age, gender, cancer type, drug therapy in metastatic patients, which lead to proper treatment of individualized patients and promote rational use of drugs by health-care professionals. This again highlights the finding that assessing and monitoring chemotherapy-induced ADR and QoL is a key measure in cancer patients.
We would like to thank Dr. Prasanna and Dr. Boaz Vincent for their unwavering support during the study and also we thankful to Universal hospital-salem and their nurses for giving their full support in data collection of this research work.
| > Conclusion|| |
In our study, 97.3% of the patients who received chemotherapy developed ADRs. Our study reveals that females are more prone to cancer. ADRs most commonly occurred in the age group of 50–59 years. Most of the patients were commonly affected by breast cancer followed by cervical cancer. Cisplatin was the common drug prescribed. Gastrointestinal tract and muscular system were the most commonly affected organ systems. Nausea and vomiting were the frequently observed ADR followed by fatigue, alopecia, and dermal reactions. In this study, 74.6% of the ADR occurred probably, followed by possible ADRs in 24.1%. Metastatic patients were found to experience greater occurrence of ADR and lesser QoL. The QoL was inversely proportional to ADR occurrence. The physical and emotional well-being were highly affected when compared to the SWB and FWB of the patient. The overall QoL improved in the 2nd review when compared to the 1st review of chemotherapy in cancer patients. This concludes that prescribing right chemotherapy which has the evidence of causing less ADR will increase the quality of treatment and QoL to cancer patients. Measures need to be put at place to reduce the physical, emotional, and economic burden on patients due to ADRs. To boost the QoL in patients, it is essential to identify and manage the ADRs by taking appropriate measures to promote judicious use of drugs.
There is a need of vigilant ADR monitoring and reporting to decrease morbidity and mortality due to ADRs, which requires further studies on larger population. The study's time period was 6 months only. It requires more time to do it in a large population.
ADRs induced by specific chemotherapeutic agents were difficult to identify when given in combination. Hence, our study could not point out the chemotherapeutic drug that causes the majority of ADRs.
The economic status of patients was not taken into consideration to assess QoL in cancer patients. Economically wealthy patients may be less affected socially and emotionally. Hence, this could make changes in QoL.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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