the Effect of ABCC2 Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin

NCT ID: NCT05494320

Last Updated: 2022-08-09

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-08-15
• Study Completion Date: 2022-12-31

Brief Summary

Study the effect of genetic polymorphism (rs1885301, rs4148396 and rs3740066) in the membrane of Multidrug resistance protein 2 (MRP2) encoded by ATP-binding cassette C2 (ABCC2) gene and its genetic expression levels on neurotoxicity in gasrtointestinal cancer patients reciving Oxaliplatin-based chemotherapy.

Detailed Description

Several solutes carriers and ATP-binding cassette transporters have been implicated in the influx or efflux of platinum-based chemotherapeutic agents such as cisplatin, carboplatin, and oxaliplatin. The ATP-binding cassette (ABC-) transporter superfamily contains several family members that may confer intrinsic or acquired multidrug resistance (MDR) by extruding anticancer agents or their metabolites from cells and suppression of such transporters may lead to sensitisation to cytostatic agents. Multidrug resistance protein 2 (MRP2), encoded by the ATP-binding cassette C2 (ABCC2) gene , is an efflux pump located on the apical membrane of many polarized cells, which transports conjugate compounds by an ATP-dependent mechanism like oxaliplatin. Single nucleotide polymorphisms (SNPs) in genes involved in drug transport like ABCC2 gene may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of Oxaliplatin-induced peripheral neurotoxicity (OXPN). Enhanced ABCC2 expression can lead to decreased cellular glutathione content. Glutathione is needed for oxaliplatin detoxification via conjugation, and it was reported that low glutathione intra- cellular levels can cause increased oxaliplatin cytotoxicity. Moreover, ABCC2 mediates the export of the oxaliplatin-glutathione conjugated form, and ABCC2 overexpressing cells were resistant to platinum derivatives.

Conditions

Gastrointestinal Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Folfox Protocol

Folfox: It includes the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.

Intervention Type: DRUG

Other Intervention Names

Folfox_6

Eligibility Criteria

Inclusion Criteria

1. gastrointestinal cancer Patients ( ≥ stages II ) who receive Oxaliplatin based chemotherapy ( FOLFOX6 ) for adjuvant and metastatic setting.

2. Eastern Cooperative Oncology Group ( ECOG ) performance ≤ 2.

3. Adequate bone marrow functions ,liver functions and renal functions.

Exclusion Criteria

1. Patients who have any clinical neuropathy.

2. Pateints with Diabetes mellitus.

3. Serious comorbid systemic disorder incompatible with study.

4. Pregnancy.

5. Other primary tumors.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Sara Mohamed Abdel Aziz Mohamed

pharmacist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nagwa Ali Sabri, Professor

Role: STUDY_DIRECTOR

Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University

May Ahmed Shawki, Lecturer

Role: STUDY_DIRECTOR

Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University

Diaa Eldin Moussa Sherif, Lecturer

Role: STUDY_DIRECTOR

Clinical oncology and nuclear medicine Department -Faculty of medicine-Ain Shams University

Sara Mohamed Abdel Aziz, Master Student

Role: PRINCIPAL_INVESTIGATOR

Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University

Locations

Ain shams university

Cairo, Abassia, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Sara Mohamed Abdel Aziz, Master Student

Role: CONTACT

dr.sara.mohamed75@gmail.com

00201119215516

May Ahmed Shawki, Lecturer

Role: CONTACT

mannus.ahmed@yahoo.com

00201001701461

Facility Contacts

Sara Mohamed Abdel Aziz

Role: primary

dr.sara.mohamed75@gmail.com

00201119215516

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Other Identifiers

279

Identifier Type: -

Identifier Source: org_study_id