Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2021 | Month : August | Volume : 15 | Issue : 8 | Page : XC01 - XC05 Full Version

Drug Utilisation Pattern and Adverse Drug Reactions in Stage II Breast Cancer Patients in a Tertiary Care Centre of Odisha- An Observational Study


Published: August 1, 2021 | DOI: https://doi.org/10.7860/JCDR/2021/48815.15281
Anima Rout, Priti Das, Ratikanta Tripathy, Dillip Kumar Agarwalla, Vedvyas Mishra

1. Assistant Professor, Department of Pharmacology, SCB Medical College, Cutttack, Odisha, India. 2. Associate Professor, Department of Pharmacology, SCB Medical College, Cutttack, Odisha, India. 3. Associate Professor, Department of Pharmacology, Kalinga Institute of Medical Science, Bhubaneshwar, Odisha, India. 4. Member Secretary, Department of Oncology, AHRCC, Cuttack, Odisha, India. 5. Tutor, Department of Pharmacology, SCB Medical College, Cuttack, Odisha, India.

Correspondence Address :
Dr. Anima Rout,
Assistant Professor, Department of Pharmacology, SCBMCH, Cuttack, Odisha, India.
E-mail: routanima3@gamil.com

Abstract

Introduction: Breast cancer is the most common cancer occurring in women with an estimated prevalence of 28.94% in Cuttack, Odisha, India. Adverse Drug Reactions (ADRs) associated with the use of anticancer drugs is a worldwide problem which needs further attention.

Aim: To know about treatment regimens, premedications used for toxicity amelioration or any associated ADRs occurring during treatment of stage II breast cancer patients.

Materials and Methods: This was a prospective observational study carried out in the Department of Pharmacology in collabo- ration with Acharya Harihar Regional Cancer Center (AHRCC), SCB Medical College and Hospital, Odisha, India. A total of 181 female breast cancer patients of stage II were finally analysed about their treatment protocol pattern including premedication, chemotherapy regimen, associated ADRs and their treatment. Different outcomes measured were Absolute Neutrophil Count (ANC), febrile neutropenia, anaemia, thrombocytopenia. ADRs were analysed by using World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) Scale and Hartwig-Siegel Scale. All analysis was performed using Statistical Package For the Social Sciences (SPSS) version 18.0.

Results: Most common chemotherapy combination regimen used was cyclophosphamide+doxorubicin+paclitaxel+trastuzumab in 30.9% of patients, out of which 28.7% showed ADRs. Ondansetron and aprepitant were commonly used as premedication in 96% of patients. Most commonly reported ADR was Chemotherapy Induced Nausea and Vomiting (CINV) in 43.6% patients and Chemotherapy Induced Neutropenia (CIN) (34.8%). Fifty percent ADRs were mild and 3.3% ADRs were severe in nature. A 64% ADRs were possible and 23% ADRs were probable according to WHO-UMC causality assessment scale. Grade 4 Neutropenia was present in 1.3% patients. Mild haematological problems were treated by blood transfusion while severe cases by additional growth factor support like Granulocyte Colony Stimulating Factor (G-CSF). In this study, mean age of presentation was found to be 44.6 years.

Conclusion: Despite use of drugs for toxicity amelioration, some grade four life threatening ADRs were observed. Mostly ADRs were missed and under-reported. Regular monitoring, increased care and patient compliance was needed to detect new ADRs and to reduce the morbidity as well as burden on the patients.

Keywords

Causality assessment, Chemotherapy, Neutropenia

Drug utilisation research has an important role in clinical practice now-a-days at both state and national level. It is the basis for formulating the strategies and policies in different hospitals or healthcare centres. The main aim of such research is facilitating rational use of drugs, utilising health resources in the best possible way, which is mostly important in a developing country like India where 72% of healthcare burden is on the patients (1).

As per Indian Council of Medical Research (ICMR), among the various cancers occurring in women, breast cancer is the most common with an estimated 1.67 million new cancer cases in 2012 (2). The estimated incidence of cancer cases in Cuttack, Odisha in 2014 was 38,375 and estimated mortality due to cancer was 16,885; amongst these, breast cancer being the leading cause of cancer in females (28.94%) (3).

The treatment of cancer aims at providing cure; if cure is not possible then palliation i.e., best possible treatment to prolong the life as much as possible (4). Chemotherapy is a part of multimodal approach for treatment of many tumours (5). It is the first approach for treatment of stage 1 and stage 2 breast cancer patients while for stage 3 and 4, mostly radiation or surgery is done (6),(7). Cell Cycle Non Specific (CCNS) drugs acts on dividing as well as resting phase of cells CCNS used in breast cancer are cyclophosphamide, doxorubicin, daunorubicin, cisplatin etc., Cell Cycle Specific (CCS) drugs acts on proliferating cells such as paclitaxel, epirubicin, 5 flurouracil etc., (8).

Chemotherapy drugs have a narrow therapeutic index. They target cancer cells and the fast-growing normal cells of skin, hair, intestine and bone marrow as well. Frequent use of chemotherapy causes CINV, alopecia, and CIN. CIN is the most common haematological toxicity (3),(8). It is especially seen with the advent of the more efficacious chemotherapeutic regimens and individual patient risk factors, example no-taxane containing regimens for breast cancer (9),(10),(11),(12).

As per World Health Organisation (WHO), ADR is defined as any response to a drug which is harmful and occurring at normal doses when used for prophylaxis, identification or treatment of disease, or for alteration of biological function in humans (13). ADR due to chemotherapy can be mild to severe and can be life threatening, so it needs further attention. Mild haematological problems due to chemotherapy are treated by blood transfusion and/or component therapy. Moderate to severe cases need additional G-CSF (14). Neutropenia associated with fever are oncological emergency and need in-patient hospitalisation and further antibiotic coverage as per Infectious Diseases Society of America (IDSA) guidelines (15). The risk of infection increases and become fatal with decreasing Absolute Neutrophil Count (ANC) i.e., in Grade 3 and grade 4 neutropenia (ANC <1000 and 500/μL, respectively) (16),(17). Such infections even when managed with only broad spectrum antibiotics can lead up to 10% in-patient mortality (16).

A very little information is available regarding patterns of care followed in breast cancer patients (5),(9),(10). Therefore, this study focused on different treatment patterns (different chemotherapy combinations used), premedication followed for toxicity amelioration, any associated ADRs during treatment protocol and their management.

Material and Methods

This was a hospital based, prospective observational study conducted at Department of Pharmacology of Sriram Chandra Bhanja Medical College and Hospital (SCBMCH), in collaboration with Department of Medical Oncology in the female ward of AHRCC, Cuttack, Odisha among breast cancer patients from November 2015 to October 2017. AHRCC is one of the 25 recognised cancer centres in India. It provides comprehensive palliative care which makes it a reliable cancer center in this zone.

Before starting the study, prior approval was obtained both from the Institutional Ethics Committee (IEC) SCBMCH and Ethics Committee of AHRCC (060-IEC-AHRCC). Written informed consent was taken from patients before including into study according to eligibility criteria.

Inclusion criteria: Female breast cancer patients of age group 18-80 years confirmed by histopathology examination done in Department of Oncopathology AHRCC or SCB Medical College Pathology laboratry were enrolled in the study. The patients were classified according to AJCC manual, 6th edition into Stage II a and II b (6).

Exclusion criteria: This study excluded pregnant women, patients who were on concomitant radiotherapy within 4 weeks of enrolment, with any other malignancies, history of bone marrow or stem cell transplantation.

Sample size calculation: Taking into account the prevalence of breast cancer among women (14%) (3), sample size has been calculated by formula which comes to 185:

n=Z21-α/2×P(1-P)/D2

Study Procedure

A total of 200 breast cancer patients were included in the study, out of which 19 were lost to follow-up and 181 patients were included in final analysis.

Data of selected and screened patients were collected in a pre-designed Case Record Form (CRF) by study group. Demographic variables including age, weight, Body Surface Area (BSA) and the treatment protocol of the patients, including pre medications, chemotherapy regimen, and cycle duration were noted. Routine laboratory investigations, i.e., Complete Blood Count (CBC) were done and other bedside parameters like Blood Pressure (BP), pulse, pallor, icterus, body temperature etc., were recorded on a daily basis during stay. Data was taken before and after every cycle of chemotherapy. Follow-up was done and patients were examined in each cycle.

Different Parameters Studied

At the end of study, ANC in each cycle, incidence of febrile neutropenia, anaemia (grade 2 and 3) and thrombocytopenia was measured. ADRs occurring during chemotherapy was also observed. ADRs were classified according to their severity by using Hartwig-Siegel Severity Assessment Scale and Causality assessment for each ADR was done by WHO-UMC causality assessment system (18),(19). Rechallenge test was done in some of the cases to assess some ADRs which were certain. Requirement of blood transfusion and/or fresh frozen plasma needed for ADR management was analysed.

The National Comprehensive Cancer Network (NCCN) guidelines were followed for all the chemotherapy regimens (7). These combination regimens were categorised in three different groups according to number of anticancer drugs in each regimen. The patient receiving two cytotoxic drugs were placed in category one, category two included patients who were on three cytotoxic drugs and Category three included patients who were on combination of two cytotoxic drugs with monoclonal antibody. Rate of neutropenia, ANC count and other haematological ADRs were assessed as per Common Terminology Criteria for Adverse Events (CTCAE V 3.0) guidelines (20).

Statistical Analysis

All the data were entered in specially designed CRF. Information was entered and analysis done by using Microsoft Excel 2010 spreadsheet. All analysis was performed using SPSS version 18.0. Categorical variables were represented as frequency and proportion. Chi-Square test was done to analyse the association of ADRs between different chemotherapy categories regimen.

Results

The total number of patients screened for the study was 200 but out of them 181 patients were found eligible for final analysis. The age distribution among patients is given in (Table/Fig 1). Most of the patients 76 (42%) were having BSA distribution less than 1.5 m2 according to which the dosage of chemotherapy regimen were calculated and given to patients.

Out of 181 patients, 165 (91%) patients have experienced at least one ADR during their treatment course. Most common regimen used in this study was doxorubicin+cyclophosphamide+ paclitaxel+ transtuzumab in 56 patients (30.9%), in which ADR was reported in 52 (28.7%) patients. Maximum number of ADRs (238 out of 843) was due to this regimen. Cyclophosphamide (C) was used in all above regimens (Table/Fig 2). Hormonal agents like tamoxifen, anastrozole were prescribed to four patients. The patients receiving two cytotoxic drugs were placed in category one (33 patients). Category two included patients who were on three cytotoxic drugs and category three included patients who were on combination of two cytotoxic drugs with monoclonal antibody (72 patients each). Among the ADRs involving gastrointestinal tract, CINV was more significant in category three patients affecting 79 (43.6%) of patients. Diarrhoea and bleeding episodes were more common in category three patients and it was statistically significant, while more episodes of neutropenia occurred in category two patients (Table/Fig 3), (Table/Fig 4).

In this study, chemotherapy induced grade 2 and grade 3 anaemia was found in 132 cycles of patients. There were 72 episodes of neutropenia, out of which 44 were of grade 3, 18 were of grade 2 and 10 episodes were of grade 4 neutropenia (Table/Fig 5).

Common premedications used were Ondansetron (96.6%) and Dexamethasone (88.4%) (Table/Fig 6). G-CSF (Filgrastim/Pegfilgrastim) were administered in total of 500 cycles for neutropenia. Blood transfusion were given to 50 patients for severe anaemia. According to WHO-UMC Category, 64% ADRs were possible and 23% ADRs were probable according to WHO-UMC Causality Assessment Scale (Table/Fig 7). 50.1 percent ADRs were mild and 3.3% ADRs were severe in nature according to Hartwig-Siegel Scale (Table/Fig 8).

Discussion

Cancer related ADRs are very common and affecting quality of life. According to literatures the highest incidence of ADRs were seen among regimen used in breast cancer patients (6),(7),(12),(21),(22). A study by Chopra D et al., has shown the incidence of ADRs as 39.1% (23). Despite regular use of premedications, the occurrences of ADRs are increasing.

The AHRCC plays a key role in cancer registry through its wide laboratory network across the country which helps to assess the cancer burden in the country (24). A total of 200 patients were screened during the course of study and in the end a total of 181 patients were included in final analysis. The mean age of presentation was 44.6 years which is less compared to other studies (25),(26). Most common chemotherapy regimen used was Cyclophosphamide+Doxorubicin+Paclitaxel+Transtuzumab. Ondansetron and dexamithasone were commonly used as premedication in many patients. Most common reported ADR was CINV, gastritis, pain,CIN etc.. Haematological system was most commonly affected. Out of all ADRs, 50% ADRs were mild. Sixty four percent ADRs were possible according to WHO-UMC Casuality Assessment Scale. There were some cases of severe Grade 4 ADRs also. ADRs were treated with different medications according to severity.

In this study, ADRs mostly occurred in the age group of 41-50 years and this finding is similar to studies by Poddar S et al., and Kirthi C et al., (14),(27). Most of the patients (42%) were having BSA distribution less than 1.5 m2 according to which the dosage of chemotherapy regimen was calculated.

Majority of patients 147 (88.3%) were started with cytotoxic drug combination of Doxorubicin and Cyclophosphamide (AC) and in later stages taxanes were added to cytotoxic combination regimen. The addition of taxanes improved the efficacy of chemotherapy, but at the cost of increased non cardiac toxicity (17),(28),(29). In this study 174 (96%) of the patients were treated with alkylating agents out of which 140 (77%) patients were on taxane-based regimen with AC. In contrast to this finding, Kumar S et al., reported that out of 500 patients, 295 (59%) received anthracycline regimen and 123 (24%) received taxane-based regimens with AC (26).

Out of 181 patients, 165 (91%) patients have experienced at least one ADR during their treatment course and this finding resembles a study by Medhi B et al., (30). As compared to studies by Poddar S et al., and Jose J and Rao P, this study also found that most commonly used class of drugs were antimetabolites and alkylating agents, which were responsible for causing ADRs (14),(15). In a study, when analysed, alkylating agents have shown ADR in 52% patients followed by antimetabolites in 20% patients (9). Trastuzumab was given to 72(39.7%) patients in this study while in other studies it was given to only 4.6% and 2% patients respectively (26),(30). Surprisingly, the results of this study resemble Medhi. B et al., who have shown that 5-FU, epirubicin, cyclophosphamide (FEC) was prescribed to 8 (4.4%) of patients and all have developed ADRs (30).

As many studies have focused on ADRs caused due to chemotherapy drugs, but there were very few studies which focus on pattern of ADRs in chemotherapy combination regimen (31),(32),(33). In this study, patients receiving chemotherapy regimen were categorised in three different groups. The patients receiving two cytotoxic drugs were placed in category one (33 patients). Category two includes patients who were on 3 cytotoxic drugs and Category three included patients who were on combination of two cytotoxic drugs with monoclonal antibody (72 patients each).

This study shows that ADRs affected haematological system most frequently followed by gastrointestinal tract and this finding is supported by Mallik S et al., and Sharma A et al., (9),(31). All the haematological ADRs 150 (72%) patients in this study were classified according to CTCAEV grading system (20). Chemotherapy kills cancer cells as well as rapid dividing normal cells of bone marrow resulting in myelosuppression thus affecting WBCs, platelets and RBCs. Among the haematological ADRs, neutropenia resulting from chemotherapy (CIN) may be life threatening. In this study CIN was more common in catagory 2 patients compared to other two groups (p-value 0.04).

Among the ADRs involving gastrointestinal tract, CINV was more significant in catagory 3 patients affecting 79 (43.3%) of patients. Chopra D et al., and Kaur K et al., in their studies have shown CINV affecting 25% and 39% of patients respectively (23),(33). Patients who received AC+T therapy (catagory 2) suffered from gastritis 70 (38%) and pain 71(39%) which is more than the catagory 1 patients. While in other study patients on AC+T Regimen complained of peripheral neuropathy, arthralgia and leucopenia (25). Neuropathy in this study was more common in patients having paclitaxel (two drugs) regimen and it was statistically significant (p-value 0.003).

Diarrhoea and bleeding episodes were more common in category three patients and it was statistically significant, while more episodes of neutropenia occurred in category two patients. In other study, 7% patients have suffered from diarrhoea (24). Alopecia was documented in 68 (37.6%) of patients in this study which was due to cytotoxic and transtuzumab therapy compared to 21% as shown by Chopra D et al., (23). Oral ulcers/stomatitis 43 (23.8%) were more in category two patients and this finding resembles Kaur K et al., (33). There should be a special mention about some ADRs due to particular drugs. Two incidence of severe hiccups due to cyclophosphamide occurred and were managed in hospital. Two cases each of granulocytosis episodes and hypotension episodes and three cases of lymphocytosis were reported in patients receiving regimen (AC+T) and ( AC+T+Tt), respectively. Four patients suffered from severe rash due to taxanes. Three patients suffered from cholelithiasis, four from breathlessness and three from colic pain during the treatment cycle.

According to literature, febrile neutropenia or Grade 3/4 neutropenia is relatively common among the haematological ADRs in breast cancer patients (23). Chemotherapy regimens have also found to induce or aggravate anaemia (23). Upto 23% of the breast cancer patients experience at least one episode of febrile neutropenia during standard chemotherapy and this figure is increased up to 98% in patients exposed to high-dose chemotherapy regimens (23). Measures were taken to overcome severe anaemia and neutropenia in these patients according to severity and chemotherapy combination profile. In this study, there were 72 episodes of neutropenia, out of which 44 were of grade 3, 18 were of grade 2 and 10 episodes were of grade 4 neutropenia as compared to Mallik S et al., who found grade 1 neutropenia as the commonest type (28.6% patients) (9). G-CSF is used both for prevention and treatment of neutropenia according to NCCN guidelines (7). Filgrastim/Pegfilgrastim were administrated in total of 500 cycles to the patients in this study. Chemotherapy induced grade 2/3 anaemia were found in 132 cycles of patients. A total of 50 (27.6%) patients were administered blood transfusion for severe anaemia. This finding is surprisingly higher in contrast to patients receiving blood transfusions (9.3%) as shown by Othieno-Abinya N et al., (34).

Different scales are available for assessing ADRs i.e., WHO-UMC system, Naranjo’s Scale (for causality assessment), Hartwig and Siegel Scale (for severity assessment) and Modified Schumock and Thornton criteria (for preventability assessment) (18),(19),(31),(35). This study shows 27 cases of severe ADRs while Chopra D et al., and Anjum F et al., have shown 764 severe cases and 1 severe case respectively (23),(25). There were 422 (50.1%) cases of mild ADRs and 394 (46.6%) cases of moderate ADRs as reported in this study. One study by Chopra D et al., was reported with 514 (86.97%) mild ADRs and 76 (12.8%) moderate ADRs (23). In this study four cases and two cases each of grade 3 and grade 4 vomiting were found, respectively. Seven cases of grade 4 diarrhoea, six cases of grade 4 constipation were also found. Causality assessment of ADRs was done using WHO-UMC assessment scale. 543 (64%) ADRs were possible, 196 (23%) were probable and 80 (9%) were certain in this study as compared to other studies where 35% and 31% of ADRs were possible, 64% and 62% of ADRs were probable and 6% ADRs were certain (30),(36). Re-challenge test was positive in some cases which makes those ADRs as certain.

The ADRs were managed with different medications. Half of the ADRs required treatment. Injection ondansetron was the most common drug used for managing the ADRs followed by filgrastrim, blood transfusion, dexamethasone, and ranitidine in this study as well as in a documented study (21). It was observed that majority of patients had received antiemetic as preventive therapy including dexamethasone (88.4%). This is consistent with findings of some other studies where majority of the cases received increased doses of antiemetic in order to manage ADR (9),(14). Nevertheless with the use of premedication, it has failed to prevent ADRs completely. This indicates that current ADR prevention and management practices require attention. Enhanced use of preventive measures and early detection of drug toxicity has the potential to contribute to reduce the severity of ADRs.

Limitation(s)

This study has not focused upon the preventability of ADRs.

Conclusion

The analysis of different treatment patterns showed that most common regimen used in the treatment of breast cancer was combination of cyclophosphamide, doxorubicin, paclitaxel and transtuzumab. The three drug regimen caused more ADRs as compared to two drug regimen. The most common ADR was CINV, but the most commonly affected system was haematological system. Despite use of drugs for toxicity amelioration, some grade 4 life threatening ADRs were observed. Many times ADRs are missed and under-reported which have affected the quality of life of patients. Regular monitoring, increase care and patient compliance is needed to reduce the morbidity and burden for patients.

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DOI and Others

10.7860/JCDR/2021/48815.15281

Date of Submission: Feb 05, 2021
Date of Peer Review: Apr 26, 2021
Date of Acceptance: Jun 17, 2021
Date of Publishing: Aug 01, 2021

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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