the Effect of ABCC2 Genetic Polymorphism on Neurotoxicity in Gastrointestinal Cancer Patients Receiving Oxaliplatin
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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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.
Study Design
Outcome Measures
Primary Outcome Measures
- neurotoxicity [6 months]
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 gastrointestinal cancer patients reciving Oxaliplatin-based chemotherapy. Grading of peripheral neuropathy using National Cancer Institute's Common Toxicity Criteria for Adverse Event ( NCI- CTCAE V5.0 ) will be assessed at baseline and before each cycle.
Eligibility Criteria
Criteria
Inclusion Criteria:
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gastrointestinal cancer Patients ( ≥ stages II ) who receive Oxaliplatin based chemotherapy ( FOLFOX6 ) for adjuvant and metastatic setting.
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Eastern Cooperative Oncology Group ( ECOG ) performance ≤ 2.
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Adequate bone marrow functions ,liver functions and renal functions.
Exclusion Criteria:
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Patients who have any clinical neuropathy.
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Pateints with Diabetes mellitus.
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Serious comorbid systemic disorder incompatible with study.
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Pregnancy.
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Other primary tumors.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Ain shams university | Cairo | Abassia | Egypt | 11566 |
Sponsors and Collaborators
- Ain Shams University
Investigators
- Study Director: Nagwa Ali Sabri, Professor, Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University
- Study Director: May Ahmed Shawki, Lecturer, Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University
- Study Director: Diaa Eldin Moussa Sherif, Lecturer, Clinical oncology and nuclear medicine Department -Faculty of medicine-Ain Shams University
- Principal Investigator: Sara Mohamed Abdel Aziz, Master Student, Clinical Pharmacy Department - Faculty of Pharmacy - Ain Shams University
Study Documents (Full-Text)
None provided.More Information
Publications
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