Effect of Copper Transporter-1 Genetic Polymorphism on Platinum Based Chemotherapy Response in Advanced Non-Small Cell Lung Cancer Patients
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Ain Shams University
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Tumor response and resistance
Study Overview
Brief Summary
Study the effect of genetic polymorphism in the membrane copper transporter 1 protein [CTR1; encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)] and its genetic expression levels on the clinical outcome of cisplatin-based regimen used in the treatment of Non-Small Cell Lung Cancer (NSCLC) in terms of :
- Treatment response : partial response (PR) / complete response (CR) and Progression-free survival (PFS)
- Treatment resistance : stationary disease (SD) or progressed disease
- Frequency and severity of regimen related toxicity
Detailed Description
The cisplatin-based regimen is an effective treatment for advanced NSCLC, showing significant beneficial outcomes such as prolong survival, improve clinical symptoms, and improve quality of life (QOL) . Although platinum-based therapy shows several benefits, but the five-year survival rate still less than 20%.
Pt resistance is an inevitable occurrence with rare exception. Aside from germ cell tumors, metastatic solid tumors are generally thought to be incurable with cytotoxic chemotherapy due to the development of resistance and subsequent disease progression.
Despite the multifactorial nature of Cisplatin resistance, intracellular accumulation of Pt appears to be a major source of drug resistance . Reduced intracellular drug accumulation is one of the most consistently identified features of cisplatin-resistant cells.
Many evidences indicated that alteration of copper transporter protein 1 (CTR1) which is the major plasma membrane transporter responsible for platinum uptake, was associated with platinum sensitivity and toxicity.
Genetic polymorphisms of CTR1 also have effects to platinum treatment response. Therefore, CTR1 might be a potential prognostic factor for survival in cancer patients underwent chemotherapy and a treatment target for overcoming platinum resistance.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Newly diagnosed with immunohistochemically and pathologically confirmed non- small cell lung cancer (NSCLC).
- •Chemotherapy naïve.
- •Age >18 years.
- •Adequate bone marrow reserve.
Exclusion Criteria
- •Presence of central nervous system metastases.
- •Inadequate liver function (bilirubin > 1.5 times upper normal limit [ULN] and alanine transaminase [ALT] or aspartate transaminase [AST] > 3.0 ULN or up to 5.0 UNL in the presence of hepatic metastases).
- •Inadequate renal function (creatinine > 1.25 times ULN, creatinine clearance < 50mL/min).
- •Serious comorbid systemic disorder incompatible with the study.
- •Second primary malignancy (except in situ carcinoma of the cervix, adequately treated basal cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior malignancy treated more than 5 years prior to enrollment without recurrence).
Outcomes
Primary Outcomes
Tumor response and resistance
Time Frame: 1 year
will be evaluated after the third (initial evaluation response) and the sixth (confirmation of initial response) chemotherapy cycle according to the new Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Secondary Outcomes
- Progression-free survival (PFS)(1.5 years)
- Regimen related toxicity(1.5 years)
Investigators
Yara Sayed Abdulwahid
Clinical Pharmacist
Ain Shams University