{"id":38985,"date":"2021-06-30T11:44:49","date_gmt":"2021-06-30T11:44:49","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=38985"},"modified":"2021-07-13T09:49:09","modified_gmt":"2021-07-13T09:49:09","slug":"pharmacovigilance-study-of-anticancer-drugs-in-a-tertiary-care-rural-hospital-in-central-india","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol14no2\/pharmacovigilance-study-of-anticancer-drugs-in-a-tertiary-care-rural-hospital-in-central-india\/","title":{"rendered":"Pharmacovigilance Study of Anticancer Drugs in a Tertiary Care Rural Hospital in Central India."},"content":{"rendered":"

Introduction<\/strong><\/p>\n

\u201cCured yesterday of my disease, I died last night of my physician.\u201d<\/p>\n

Matthew Prior, from \u201cThe Remedy Worse than the Disease\u201d (1714).<\/strong><\/p>\n

The main aim of pharmacovigilance is to reduce the risk of drug related problems to the patient. The information generated by pharmacovigilance is useful in educating doctors about adverse drug reactions (ADRs) and in the official regulation of drug use[1]<\/sup>. A study conducted in USA showed that adverse drug events extended the hospital stay, increased hospitalization cost and increased the risk of death nearly two-fold.[2]<\/sup> In India too, ADRs are increasing and is a great concerned of health, increased hospitalization and cost.[3]<\/sup> One study conducted among patients of Medicine Dept. showed incidence of ADRs 1.8%[4]<\/sup> while another study showed that Incidence of ADRs is 4.75%.[5]<\/sup><\/p>\n

Chemotherapy is a part of the multimodal treatment of cancer, thus allowing for more limited surgery and even cure of formerly incurable cases. [6]<\/sup> Chemotherapy regimens are immensely complex and susceptible to errors.[7]<\/sup> Due to the narrow therapeutic index of anticancer drugs, multiple combinations of drug and the dosage required to achieve a therapeutic response frequently proves toxic to the body\u2019s rapidly proliferating cells.[8]<\/sup>A pharmacovigilance study conducted by Couffignal Al et. al. in a French oncology institute showed that there is a high incidence and economic burden of ADR related to cancer chemotherapy.[9]<\/sup> One study from South India shows that ADRs reported in Oncology Department is the second highest percentage after general medicine.[10]<\/sup><\/p>\n

It is well accepted that anticancer agents are associated with severe adverse effects, decreased the quality of life, and causes an economic burden on patients. No extensive published data is available in Indian population regarding the ADRs of cancer chemotherapy. So, the present study has been undertaken to<\/p>\n

Estimate the pattern of ADRs of intravenous(i.v.) anticancer drugs.<\/p>\n

Assess the causality of ADRs.<\/p>\n

Assess the severity of ADRs.<\/p>\n

This study will create a safety profile of anticancer drugs representing central India.<\/p>\n

Material and Methods<\/strong><\/p>\n

Study design<\/strong><\/p>\n

The study was planned as a single-centric prospective observational cross-sectional survey.<\/p>\n

Setting<\/strong><\/p>\n

This study was conducted in the Department of Pharmacology and Radiotherapy of Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra over a period of 18 months from 1st<\/sup> January 2015 to 30th<\/sup> June 2016.<\/p>\n

Study population<\/strong><\/p>\n

The indoor patients who were diagnosed to have cancer and receiving i.v anticancer drugs during the study period.<\/p>\n

The following recruitment criteria were used:<\/p>\n

Inclusion criteria<\/strong><\/p>\n

Patients diagnosed to have cancer.<\/p>\n

Patients receiving i.v. anti-cancer drugs.<\/p>\n

Patients of either gender above 18 years of age.<\/p>\n

Exclusion criteria:<\/strong><\/p>\n

Patients not willing to give written informed consent.<\/p>\n

Patients on concurrent Radiotherapy.<\/p>\n

Patients with altered hepatic or renal parameters prior to chemotherapy.<\/p>\n

Patients who are taking the alternative system of medicines like Ayurveda, Homeopathy, Unani etc.<\/p>\n

Mentally retarded patients.<\/p>\n

Drug addicts.<\/p>\n

Unconscious and patients unable to respond to verbal questions.<\/p>\n

Sampling procedure<\/strong><\/p>\n

Convenience sampling was used to select the study sample.<\/p>\n

Sample size<\/strong><\/p>\n

The sample size was calculated by using following formula for cross-sectional study.<\/p>\n

Formula: Sample size =<\/p>\n

\"Vol14No2_Pha_Dip_eq1\"<\/a><\/p>\n

Where Z= Z value that is 1.96 at 95% confidence interval, p= proportion, q= (1-p), d= \u03b1 error<\/p>\n

Using previous studies knowledge[11]<\/sup>, proportion of ADR due to anticancer drug is 41.67%, 95% Confidence Interval with 5% absolute error or precision<\/p>\n

In this study, Sample size\u00a0=<\/strong><\/p>\n

\"Vol14No2_Pha_Dip_eq2\"<\/a><\/p>\n

Data Collection<\/strong><\/p>\n

Data were recorded in the Case Record Form. Patient details, chemotherapy details and pattern of ADRs were collected and the data were documented as per study proforma. Haematological and biochemical tests that were performed during chemotherapy as a part of treatment protocol were noted. The details of ADRs which were present at the time of visit or occurred within one-month (to avoid recall bias) were noted in the ADR Reporting Form.<\/p>\n

The ADRs encountered in the study population were classified depending on the various body systems involved. Causality was evaluated as per World Health Organization – Uppsala Monitoring Centre causality assessment scale [12]<\/sup>.<\/strong>The severity of the ADRs was evaluated by Modified Hartwig and Siegel scale[13,14]<\/sup><\/p>\n

Statistical Analysis<\/strong><\/p>\n

Patient\u2019s details (gender & age), site of malignancy wise distribution, different groups of anticancer drugs prescribed, age-wise & system wise distribution of ADRs, causality & severity of ADRs are represented as percentage. Odds ratio was calculated to assess the relationship between the profile of patient and the system wise ADRs. Statistical significance was determined at 95% level of confidence.<\/p>\n

Human subject protection<\/strong><\/p>\n

Approval of the Institutional Ethics Committee was taken before commencing the study. Patients were included in the study after a written, informed consent. Confidentiality of the patient’s identity was maintained.<\/p>\n

Results<\/strong><\/p>\n

Characteristics of study population are shown in table-1.<\/strong><\/p>\n

A total of 374 patients on cancer chemotherapy were included in the study. Out of 374 cases 210 (56.15%) were females, 164 (43.85%) were males. Large no. of cases i.e. 121(32.35%) were from 41 to 50 yrs age group followed by 92(24.60%) from 51 to 60 yrs age group. Oral carcinoma was the commonest type found in 124 (33.16%) cases, followed by breast carcinoma (20.32%) and cervical carcinoma (10.70%). A total of 780 no. of anticancer drugs were received by the patients out of which 311 (39.87%) were alkylating agents followed by natural products 266(34.10%). ADR was seen in 293(78.34%) patients, whereas 81(21.66%) cases were without any ADR. Out of 293 patients with ADRs, 168 cases were female and 125 cases were male. Highest number i.e. 92(31.40%) cases with ADR were between 41 to 50 yrs and least number i.e. 20(6.83%) ADR cases were between 18 to 30 yrs of age.<\/p>\n

Table 1: Characteristics of study population.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Characteristics<\/strong><\/td>\nCategories<\/strong><\/td>\nNo. of patients\/drugs (%)<\/strong><\/td>\nADR cases (%)<\/strong><\/td>\n<\/tr>\n
Gender <\/strong><\/td>\nMale<\/td>\n164(43.85)<\/td>\n125(42.66)<\/td>\n<\/tr>\n
Female<\/td>\n210 (56.15)<\/td>\n168(57.34)<\/td>\n<\/tr>\n
Age (years)<\/strong><\/td>\n18 to 30<\/td>\n22(5.88)<\/td>\n20(6.83)<\/td>\n<\/tr>\n
31 to 40<\/td>\n64(17.11)<\/td>\n50(17.06)<\/td>\n<\/tr>\n
41 to 50<\/td>\n121(32.35)<\/td>\n92(31.40)<\/td>\n<\/tr>\n
51 to 60<\/td>\n92(24.60)<\/td>\n71(24.23)<\/td>\n<\/tr>\n
> 60<\/td>\n75(20.05)<\/td>\n60(20.48)<\/td>\n<\/tr>\n
Site <\/strong><\/p>\n

of <\/strong><\/p>\n

malignancy <\/strong><\/td>\n

Oral<\/td>\n124 (33.16)<\/td>\n<\/td>\n<\/tr>\n
Breast<\/td>\n76(20.32)<\/td>\n<\/td>\n<\/tr>\n
Cervix<\/td>\n40(10.70)<\/td>\n<\/td>\n<\/tr>\n
Lungs<\/td>\n21(5.61)<\/td>\n<\/td>\n<\/tr>\n
Rectum<\/td>\n18(4.81)<\/td>\n<\/td>\n<\/tr>\n
Larynx<\/td>\n14(3.74)<\/td>\n<\/td>\n<\/tr>\n
Oesophagus<\/td>\n13(3.48)<\/td>\n<\/td>\n<\/tr>\n
Colon<\/td>\n11(2.94)<\/td>\n<\/td>\n<\/tr>\n
Ovary<\/td>\n9(2.41)<\/td>\n<\/td>\n<\/tr>\n
Testis<\/td>\n9(2.41)<\/td>\n<\/td>\n<\/tr>\n
NH Lymphoma<\/td>\n9(2.41)<\/td>\n<\/td>\n<\/tr>\n
Sarcoma<\/td>\n7(1.87)<\/td>\n<\/td>\n<\/tr>\n
H. Lymphoma<\/td>\n4(1.07)<\/td>\n<\/td>\n<\/tr>\n
M. Myeloma<\/td>\n4(1.07)<\/td>\n<\/td>\n<\/tr>\n
Gall Bladder<\/td>\n4(1.07)<\/td>\n<\/td>\n<\/tr>\n
Occult Primary<\/td>\n4(1.07)<\/td>\n<\/td>\n<\/tr>\n
Ear<\/td>\n3(0.80)<\/td>\n<\/td>\n<\/tr>\n
Stomach<\/td>\n2(0.53)<\/td>\n<\/td>\n<\/tr>\n
Bladder<\/td>\n2(0.53)<\/td>\n<\/td>\n<\/tr>\n
Groups of anticancer drugs prescribed<\/strong><\/td>\nAlkylating Agents<\/td>\n311(39.87)<\/td>\n<\/td>\n<\/tr>\n
Natural Products<\/td>\n266(34.10)<\/td>\n<\/td>\n<\/tr>\n
Antimetabolites<\/td>\n152(19.49)<\/td>\n<\/td>\n<\/tr>\n
Immunostimulant & Biological Response Modifiers<\/td>\n36 (4.62)<\/td>\n<\/td>\n<\/tr>\n
Miscellaneous Agents<\/td>\n8(1.03)<\/td>\n<\/td>\n<\/tr>\n
Hormones and Hormones antagonist<\/td>\n7(0.90)<\/td>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Out of 812 no. of ADRs, most ADRs i.e. 419(51.60%) were G.I. system related, followed by skin and appendages related ADRs [194(23.88%)] \u00a0and least no. of ADRs i.e. 2(0.25%) were related with cardiovascular system (shown in table-2). The association of female in developing haematological ADRs are statistically significant (p<0.05) .<\/p>\n

Table 2: System wise distribution of ADRs.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
System<\/strong><\/td>\nNo. of ADRs<\/strong><\/td>\nPercentage<\/strong><\/td>\n<\/tr>\n
Gastrointestinal System<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Anorexia<\/td>\n125<\/td>\n15.39%<\/td>\n<\/tr>\n
Nausea<\/td>\n112<\/td>\n13.79%<\/td>\n<\/tr>\n
Vomiting<\/td>\n69<\/td>\n8.50%<\/td>\n<\/tr>\n
Diarrhoea<\/td>\n40<\/td>\n4.93%<\/td>\n<\/tr>\n
Constipation<\/td>\n36<\/td>\n4.43%<\/td>\n<\/tr>\n
Mouth ulcer<\/td>\n12<\/td>\n1.48%<\/td>\n<\/tr>\n
Pain abdomen<\/td>\n10<\/td>\n1.23%<\/td>\n<\/tr>\n
Dysphagia<\/td>\n5<\/td>\n0.62%<\/td>\n<\/tr>\n
Heart burn<\/td>\n4<\/td>\n0.49%<\/td>\n<\/tr>\n
Hematemesis<\/td>\n3<\/td>\n0.37%<\/td>\n<\/tr>\n
Halitosis<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Hiccup<\/td>\n1<\/td>\n0.12%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n419<\/strong><\/td>\n51.60%<\/strong><\/td>\n<\/tr>\n
Skin and Appendages<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Alopecia<\/td>\n146<\/td>\n17.98%<\/td>\n<\/tr>\n
Hyperpigmentation<\/td>\n36<\/td>\n4.43%<\/td>\n<\/tr>\n
Skin rash<\/td>\n4<\/td>\n0.49%<\/td>\n<\/tr>\n
Blackish tongue<\/td>\n3<\/td>\n0.37%<\/td>\n<\/tr>\n
Blackish nail<\/td>\n3<\/td>\n0.37%<\/td>\n<\/tr>\n
Lips swelling<\/td>\n1<\/td>\n0.12%<\/td>\n<\/tr>\n
Thrombophlebitis<\/td>\n1<\/td>\n0.12%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n194<\/strong><\/td>\n23.88%<\/strong><\/td>\n<\/tr>\n
Haematology<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Anaemia<\/td>\n57<\/td>\n7.02%<\/td>\n<\/tr>\n
Leucopenia<\/td>\n22<\/td>\n2.71%<\/td>\n<\/tr>\n
Thrombocytopenia<\/td>\n17<\/td>\n2.09%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n96<\/strong><\/td>\n11.82%<\/strong><\/td>\n<\/tr>\n
General<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Weakness<\/td>\n14<\/td>\n1.72%<\/td>\n<\/tr>\n
Body ache<\/td>\n9<\/td>\n1.11%<\/td>\n<\/tr>\n
Fever<\/td>\n7<\/td>\n0.86%<\/td>\n<\/tr>\n
Vertigo<\/td>\n5<\/td>\n0.62%<\/td>\n<\/tr>\n
Burning sensation whole body<\/td>\n4<\/td>\n0.49%<\/td>\n<\/tr>\n
Generalized oedema<\/td>\n3<\/td>\n0.37%<\/td>\n<\/tr>\n
Dryness of mouth<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Swelling of legs<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Rhinorrhoea<\/td>\n1<\/td>\n0.12%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n47<\/strong><\/td>\n5.79%<\/strong><\/td>\n<\/tr>\n
Musculoskeletal System<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Leg cramps<\/td>\n24<\/td>\n2.96%<\/td>\n<\/tr>\n
Joint pain<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n26<\/strong><\/td>\n3.21%<\/strong><\/td>\n<\/tr>\n
Central Nervous System<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Headache<\/td>\n10<\/td>\n1.23%<\/td>\n<\/tr>\n
Sleeplessness<\/td>\n7<\/td>\n0.86%<\/td>\n<\/tr>\n
Paraesthesia<\/td>\n6<\/td>\n0.74%<\/td>\n<\/tr>\n
Drowsiness<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n25<\/strong><\/td>\n3.08%<\/strong><\/td>\n<\/tr>\n
Ocular<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Pain in eyes<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Blurring of vision<\/td>\n1<\/td>\n0.12%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n3<\/strong><\/td>\n0.37%<\/strong><\/td>\n<\/tr>\n
Cardiovascular System<\/strong><\/td>\n<\/td>\n<\/td>\n<\/tr>\n
Palpitation<\/td>\n2<\/td>\n0.25%<\/td>\n<\/tr>\n
Total<\/strong><\/td>\n2<\/strong><\/td>\n0.25%<\/strong><\/td>\n<\/tr>\n
Total No. of ADRs<\/strong><\/td>\n812<\/strong><\/td>\n\u00a0<\/strong><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Out of 293 patients with ADR, the combination of cisplatin, paclitaxel and 5-fluorouracil caused ADRs in 58(19.80%) patients followed by 51(17.41%) ADR cases caused by cisplatin alone depicted in Fig.1. The association between skin & appendages disorders and combination therapy is very highly significant (p<0.0001). The musculoskeletal ADRs are also significantly (p<0.05) more common with combination therapy.<\/p>\n\n\n\n
\"Vol14No2_Pha_Dip_fig1\"<\/a><\/td>\nFigure 1: Distribution of ADR cases according to Monotherapy\/Combination therapy.<\/strong><\/p>\n

Click here to view figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Causality & severity Categories of ADRs are shown in table-3.<\/strong><\/strong><\/p>\n

Table 3: <\/strong>Causality and severity Categories of ADRs<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
\u00a0<\/strong><\/td>\nCategories<\/strong><\/td>\nNo. of\u00a0 cases (%)<\/strong><\/td>\n<\/tr>\n
\u00a0<\/strong><\/p>\n

\u00a0<\/strong><\/p>\n

Causality<\/strong><\/td>\n

Certain<\/td>\n0(0.00)<\/td>\n<\/tr>\n
Probable\/Likely<\/td>\n81(9.98)<\/td>\n<\/tr>\n
Possible<\/td>\n731(90.02)<\/td>\n<\/tr>\n
Unlikely<\/td>\n0(0.00)<\/td>\n<\/tr>\n
Conditional\/Unclassified<\/td>\n0(0.00)<\/td>\n<\/tr>\n
Unassessable\/Unclassifiable<\/td>\n0(0.00)<\/td>\n<\/tr>\n
\u00a0<\/strong><\/p>\n

Severity<\/strong><\/td>\n

Mild<\/td>\n712(87.68)<\/td>\n<\/tr>\n
Moderate<\/td>\n93(11.45)<\/td>\n<\/tr>\n
Severe<\/td>\n7(0.86)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

731(90.02%) ADRs had been categorized as \u2018possible\u2019 whereas the remaining 81(9.98%) ADRs had been categorized as \u2018probable\/likely\u2019. The association of G.I & haematology related ADRs with the causality (probable & possible) was highly significant (p<0.01). Out of 812 ADRs, most ADRs i.e. 712(87.68%) were found in mild category followed by 93(11.45%) ADRs were in moderate category and 7(0.86%) were in severe category. The mild reactions were more common in G.I & haematology related ADRs as compare to moderate & severe category (p<0.05).(shown in table-4)<\/p>\n\n\n\n
\"Vol14No2_Pha_Dip_Tab4\"<\/a><\/td>\nTable 4:<\/strong> Determinants of various types of ADRs among study subjects.<\/strong><\/p>\n

Click here to view table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Discussion<\/strong><\/p>\n

ADRs are negative effects of drug therapy which will lead to increased health care costs, increased physician visits, diminished quality of life, hospitalizations, and even death.[14]<\/sup> Jose et al.[10]<\/sup> showed that among all classes of drugs anticancer drugs cause most of ADRs.[10]<\/sup> Over the past few decades, newer anticancer agents have added to the treatment of cancer but simultaneously increased the incidence of ADRs. So, the documentation and reporting of ADRs become an essential element in exploring the side effect profile of a drug. It is possible only by an extensive drug safety monitoring program[15]<\/sup>.<\/p>\n

Our \u00a0study shows that oral carcinoma is the commonest(33.16%)\u00a0 type of cancer in central India which correlates with the study findings of\u00a0 Bellare et al.[16]<\/sup> and Rao et al.[17]<\/sup> conducted in South India. As far as prescription of drugs is concerned, alkylating agents were most frequently(39.87%) used anticancer drugs followed by natural products (34.10%). Sharma et al.[18]<\/sup> also \u00a0found that alkylating agents were mostly used.<\/p>\n

In this study, ADRs were found in 78.34% cases which is similar to the \u00a0finding (70%) of Goyal et al.[19]<\/sup> In contrast to our study, \u00a0Khandelwal et al.[20]<\/sup> found that only 37.70% cases were suffering from ADRs. We found that out of all ADR cases, females(57.34%) suffered more in comparison with males(42.66%) which is almost similar to the findings (55.9% female) of Sharma et al. [18]<\/sup> In our study, more no. of\u00a0 ADRs (31.40%) \u00a0were found in between 41 to 50 yrs of age which is comparable (27.4%) to the findings of Chopra et al.[21]<\/sup>. In contrast to our study Mallik et al.[11]<\/sup> found that highest no. of ADR cases (40%) occurred in 61 to 70 yrs group. We found least no. of ADR cases i.e. 6.83% in 18 to 30 yrs group which is similar to the result of Poddar et al.[22]<\/sup> \u00a0The most commonly affected system by anticancer drugs was G.I. system(51.60%) followed by skin and appendages (23.88%). Similarly Chopra et al.[21]<\/sup> found that highest no. of ADRs were G.I.T. related(43.7%) followed by skin and appendages related(24.9%). On the contrary, Mallik et al.[11]<\/sup> found hematological system to be the most frequently involved followed by G.I.T. In the present study, we have found that haematological ADRs are more common in female. \u00a0Alopecia was the most common (17.98%) ADR followed by anorexia (15.39%), nausea (13.79%) and vomiting (8.50%). In a similar study by Wahlang et al.[23]<\/sup>\u00a0 also found highest no. of alopecia patients, followed by vomiting, constipation, anorexia. Prasad et al.[22]<\/sup> \u00a0found nausea and vomiting as most common ADRs, whereas Gunaseelan et al.[24]<\/sup> reported the same as less common.[24]<\/sup> Patients on monotherapy had 74 ADR cases out of which 68.92% cases of ADRs were caused by cisplatin followed by paclitaxel (12.16%). Anorexia, constipation, anemia, leukaemia & weakness were frequently seen in cisplatin treated patients. \u00a0In a similar study Goyal et al.[19]<\/sup>\u00a0 showed that the most common individual drug responsible for ADR was cisplatin (45%). The combination of cisplatin, paclitaxel and 5-fluorouracil caused maximum number (26.48%) of ADRs followed by the combination of epirubicin and paclitaxel (15.99%). The skin and appendages related ADRs & musculoskeletal ADRs were significantly(p<0.05) associated with combination therapy. Gunaseelan et al.[24]<\/sup> reported that cisplatin was the most common individual drug causing ADRs either alone or in combination. Colon carcinoma was treated by the combination of leucovorin, oxaliplatin and 5 fluorouracil (FOLFOX regimen). The FOLFOX regimen produced lower rates of severe anorexia, anemia, rash and \u00a0diarrhoea which is comparable with the finding of Goldberg RM et al. [25]<\/sup><\/p>\n

As per WHO-UMC causality assessment, our study revealed that most of the ADRs were under ‘possible’ category (90.02%). The remaining ADRs (9.98%) were under ‘probable\u2019 category. The G.I.T. & haematology related ADRs were significantly (p<0.01) more common under \u2018possible\u2019 category. In consistent with our finding Chopra et al.[21]<\/sup> and Bellare et al.[16]<\/sup>\u00a0 revealed that most of the ADRs were \u201cpossible\u201d followed by \u201cprobable\u201d category. On contrary to our study Amartya De[3]<\/sup>\u00a0 reported 85.28% were probable, 12.88% were possible and about 1.84% were certain ADRs. Most of the chemotherapy in our study was comprised of more than a single drug. Thus, multiple drugs developed a causal link for a ADR. So, most of the causality assessment in our study has been classified as \u201cpossible\u201d. Previous studies showed that causality assessment of ADR is a subjective, imprecise and low level of agreement exists between two observers.[26,27]<\/sup> This may be the cause for the difference among various studies. In this study, severity assessment was evaluated by using modified Hartwig and Siegel scale which showed most of the cases were under \u2018mild\u2019(87.68%) \u00a0category followed by \u2018moderate\u2019(11.45%) and \u2018severe\u2019 (0.86%) category which were comparable with the result of Chopra et al.[21]<\/sup> This shows that ADRs are due to cancer chemotherapy are rarely life threatening with early detection and appropriate pre-medications. The mild reactions were significantly(p<0.05) more common in G.I.T. & haematology related ADRs.<\/p>\n

Conclusion<\/strong><\/p>\n

Gastrointestinal system ADRs are the most commonly observed ADRs in cancer chemotherapy. The patients receiving anticancer drugs should be closely monitored for development of any ADR. Pharmacovigilance is an essential tool which can identify the ADRs of cancer chemotherapy by regular monitoring of clinical and laboratory findings. Prompt detection of ADR is important to reduce morbidity and mortality. All ADRs cannot be prevented but their incidence can be decreased by timely use of various medications. There is a high necessity for patient counselling about the therapy and possible ADRs during treatment and also encouraging the treating physicians to report all ADRs irrespective of their severity which can definitely be able to safeguard the health of our population.<\/p>\n

Acknowledgement<\/strong><\/p>\n

Authors would like to acknowledge the HOD, Department of Pharmacology and HOD, Department of Radiotherapy, Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, Maharashtra for providing the necessary facilities to carry out this study.<\/p>\n

Conflict of interest<\/strong><\/p>\n

There is no conflict of interest in this study.<\/p>\n

Funding source<\/strong><\/p>\n

The study received no grants from any funding agency or sectors.<\/p>\n

References<\/strong><\/p>\n

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