Study of ABCB1,SLC22A16 Drug Transporter Genes and Doxorubicin and Cyclophosphamide Toxicity in Brest Cancer Patient

November 29, 2020 updated by: Damanhour University

Associations Between Genetic Polymorphisms of Drug Transporter Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast Cancer Patients

polymorphisms of drug transporter genes may influence of Doxorubicin-Cyclophosphamide toxicity in breast cancer patients.

the investigators want to

evaluate the association between associations between genetic polymorphisms of ABCB1,SLC22A16 Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast Cancer Patients treated by Doxorubicin-Cyclophosphamide regimen therapy

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

breast cancer is the most common cancer diagnosed in women .Breast cancer can occur in both men and women, but it's far more common in women.

The etiology of breast cancer possesses a multifactorial origin , showing as risk factors reproductive age, early menarche, late menopause, nulli parity, exogenous hormones ,smoking, obesity, diet, alcohol consumption, physical inactivity, and genetic and environmental factors(1).

Chemotherapy combination usually used in treat breast cancer specially cyclophosphamide which is alkylating agent and doxorubicin which is cytotoxic drug.

Doxorubicin entry to the cell is facilitated by the solute importer SLC22A16,the efflux of AC drugs uses several ATP-binding cassette transporters (ABC),( ABCB1, ABCC1, ABCC2, ABCG2)(2),(7).

Most chemotherapeutic agents are not specific against neoplastic cells , also affecting normal cells. Which result in a wide range of adverse reactions in virtually all tissue of body. Unfortunately, chemotherapy-induced toxicities are commonly affecting cancer patients with various intensity, and could be the reason for treatment delays and significantly lowered quality of life. Hematological and gastrointestinal toxicities are common in patients treated with cyclophosphamide and doxorubicin(3).

Extremely high proliferative capacity of hematopoietic system makes it the collateral target for chemotherapeutic agents. Chemotherapy-induced neutropenia are , because of the high susceptibility of neutrophil lineage to cytotoxic effects of cancer treatment. The drug-induced destruction of neutrophil precursors in bone marrow is the main cause of those symptoms. Decrease in neutrophil count is managed by the dose reduction and delays that decrease the dose intensity, where is maintaining the dose is important for favorable response to treatment(3). Another frequent and serious myelotoxic symptom in breast cancer chemotherapy is anemia. This condition may emerge from the disease itself, but the effect of concomitant administration of cytotoxic drugs is also the cause of drop in the hemoglobin level. Anemia has deleterious effect on patients' quality of life as well as on the treatment response. The suspected causes include blood loss, reduced or impaired erythrocytes production and high rate of red blood cells destruction or their reduced survival(4).

Chemotherapy-induced nausea and vomiting (CINV) is a common severe side effect for cancer patients undergoing emetic chemotherapy. The complete pathophysiology of CINV is not known but gastrointestinal (GI) side effects associated with anticancer chemotherapy are traditionally thought to be attributable to mucosal damage.

Nausea is complex in nature and probably depending on more than one etiological factor . Different pathways have been identified for acute and delayed CINV Also, nausea and vomiting can result in anorexia, decreased performance status, metabolic imbalance, wound dehiscence, esophageal tears and nutritional deficiency(5).

In the study we will focuse on the analysis of the relations between the polymorphic variants in some drug transporter genes with known or potential role in the AC-induced toxicity. Single nucleotide polymorphisms will analyzed in genes encoding proteins Involved in AC drug transport

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 11651
        • Recruiting
        • Elhussien University Hospital
        • Contact:
        • Contact:
          • wael elshishtawy, Ass.prof
          • Phone Number: 00201119888618

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

all breast cancer females reciving (Ac regimen) at El-hosien University Hospital

Description

Inclusion Criteria:

  1. women who has confirmed diagnosis of breast cancer.
  2. patient who will be treated with cyclophosphamide and doxorubicin(AC) regimen only .
  3. patient take drug regimen for first time.

Exclusion Criteria:

- 1. Patients with metastatic disease and with other previous tumors were excluded from this study 2. Pregnant or nursing female. 3. The patients who were diagnosed with cardiovascular disease or with low left ventricular ejection fraction.

4 .patients who had benign breast cancers, or had no clinical pathological information

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
.1-The frequency of the genetic polymorphisms of ABCB1 in breast cancer patien
Time Frame: up to 24 week
the blood samples will be DNA extracted using DNA extraction kit then single nucleotide polymorphisms of CYP2C19 gene will be detected by real time PCR
up to 24 week
The frequency of the genetic polymorphisms of SLC22A16 in breast cancer patients
Time Frame: up to 24 week
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of SL22A16 gene will be detected by real time PCR
up to 24 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between genetic polymorphisms of ABCB1 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time Frame: up to 24 week
the blood samples will be DNA extracted using DNA extraction kit then single nucleotide polymorphisms of ABCB1 gene will be detected by real time PCR
up to 24 week
Correlation between genetic polymorphisms of SLC22A16 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time Frame: up to 24 weeks
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of SL22A16 gene will be detected by real time PCR
up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Damanhour University

Collaborators

Al-Azhar University

Investigators

  • Study Director: Hoda salem, Ass.prof, Faculty of pharmacy Al-Azhar University for Girls
  • Principal Investigator: Wael helmy, Ass.prof, Faculty of medicine Al-Azhar University for Boys
  • Principal Investigator: Amira bisheer, PhD, faculty of pharmacy ,Damanhour University
  • Principal Investigator: sanaa mohsen, B.pharm, faculty of pharmacy,Al-Azhar University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2020

Primary Completion (Anticipated)

February 1, 2021

Study Completion (Anticipated)

February 1, 2021

Study Registration Dates

First Submitted

April 29, 2020

First Submitted That Met QC Criteria

November 29, 2020

First Posted (Actual)

December 4, 2020

Study Record Updates

Last Update Posted (Actual)

December 4, 2020

Last Update Submitted That Met QC Criteria

November 29, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0000012

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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