Pharmacogenomics

Case study

A qualitative study on chemotherapy induced adverse drug reactions- Potential clinical         implementation of cancer pharmacogenomics in its prevention.

                                                 Aarthy Palani

Completed in partial fulfillment of the requirement for

HA 5301: Healthcare Administration Research Methods

 Texas State University

12-12-2016

Abstract

Background: Over the past forty years, the survival rate of cancer patients was increased from 50% to 70% in the nation (American Cancer Society), however, the survivor’s quality of life was greatly impaired by irreversible and life-threatening conditions due to the side effects caused by cancer medications.  

Aim: To analyze the incidence and severity of adverse drug reaction (ADR) induced by chemotherapeutic agents; the influence of clinical implementation of cancer pharmacogenomics (PGx) in preventing the serious side effects and in safer personalized drug delivery in cancer patients.

Methods: The study population has been recruited from an oncology department of tertiary care hospital in Texas.  The patients who were treated with chemotherapy and reported with the incidence of ADR were recruited and categorized into five different focus groups based on age ranges (n=40).  Impact of four specific chemotherapeutic agents were assessed in focus groups for causation of ADR.  The number of adverse event reports was collected from VigiAccess database and through semi structured interviews. The severity and preventability of ADR was determined using modified Hart wig and modified Schumock-Thornton scale respectively. Hap Map was employed to determine interindividual genetic variation and their response to a drug.

Results: The most common side effects were infections, nausea/vomiting, hair loss, gonadal dysfunction, myelosuppression, hypersensitivity and impaired sensory function.  Of many factors contributing to ADR, genetic polymorphism plays a key role in variation of drug response.  Through implementation of clinical pharmacogenomics more personalized medicine can be prescribed which would drastically decrease the ADR occurrence.

Keywords: Chemotherapy, ADR, Genetics, Prevention, Clinical Pharmacogenomics.

Introduction

The World Health Organization(WHO) defines ADR as “a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function.”  In USA, severe ADR remains the fourth to sixth major cause of death and a major reason for post-marketing drug withdrawal from the public use (Laurent Becquemont 2009).  In 2010, the annual medical expense of ADR in American society was estimated to be $136 billion, which was greater than the total cost of cardiovascular care (Johnson JA et al, 1995).  The antineoplastic group of drugs was considered the most significant agent causing ADR due to its long-term administration.  Everyone is genetically unique and this forms the basis for varied drug responses with the optimal drug and dosage in two different patients.  There comes the role of pharmacogenomics, the technology or study that analyses how genetic make-up of the individual affects his/her response to a drug (Ermack Gennady,2015).  Pharmacogenomic research enables the potential identification of patients who are likely to respond to medication and/or those who have probability of developing severe adverse drug reactions to the therapeutic dose of same medication (Adam Stevens et al, 2013).  This study was done to gain in-depth knowledge of genetic predisposition to ADR occurrence and the perspective of cancer survivors in the acceptance of clinical pharmacogenetic testing towards the use of “personalized medicine”.

Literature review

Thorough review of various prior research works has demonstrated that chemotherapeutic induced ADRs were highly catastrophic and genetics play a key role in exhibiting variations of drug response of individual genetic make-up.  In a recent study, the global pattern of ADRs were documented, which revealed increased number of ADRs was reported for antineoplastic and immunomodulating agents in high income and developed nations of the world (Aagaard et al,2009).  According to Phillips et al (2001), in more than 50% of drugs, genetic variability at least in one of the enzymes associated with altered drug metabolism, was responsible for the development of such ADR.  In a pharmacogenetic study, conducted by patient’s genetic component and drug metabolizing pathway received a higher priority score in the occurrence of ADR (Kaitlyn Shaw et al 2013).  The search terms used were Chemotherapy induced ADR, cancer pharmacogenomics, interindividual genetic variation in drug response.

Methodology

 Sampling

The study was conducted on patients admitted to the Cancer center of Houston Methodist hospital, a tertiary care hospital located in Texas.  The hospital provides varied cancer treatment including surgery and chemotherapy for all age groups.  In this study design, purposive sampling method was used to recruit participants for focus groups.  The demographic details (age and gender), family and medical history including previous drug response and drug interaction was noted from hospitals electronic health record system with assistance from physicians and other health professionals.  Ethical clearance was received from Institutional Review Board (IRB) before conducting interviews as the study deals with sensitive patient medical information.  The desired participants were contacted through small brochures and posters displayed in the hospital premises.  Before participation, complete details of the study purpose were explained and willingness of the participants was confirmed by signed informed consent.  Patients of both genders above 35 years of age, diagnosed with cancer and developed under chemotherapeutic treatment were included in the study.  The exclusion criteria included patients who reported ADR due to blood product transfusion, intentional over dose, medical error and those with history of drug allergy.

        The participants were categorized into five focus groups based on age ranges: Focus group I (35-44 years), focus group II (45-54 years), focus group III (55-64 years), focus group IV (65-74 years) and group V (above 75 years).

Data Collection:

  Among large number of effective chemotherapeutic agents administered for cancer treatment, the ones found to cause major and frequent ADRs were taken for this study purpose.  The chemotherapeutic drugs for which there was maximum number of ADR being reported was collected from VigiAccess database, WHO Collaborating Centre for International Drug Monitoring, which was then used as a tool in comparison with the focus group.  The highest incidence of ADR reporting was associated with methotrexate (24913 reports), paclitaxel (24507 reports) carboplatin (16252 reports), and cisplatin (16053 reports).  The study participants who were under therapy with these drugs was observed for incidence of ADR which would be assessed for similarity.