Concurrent Chemotherapy and Radiotherapy With Nitroglycerin in Patients With Locally Advanced Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
Nitroglycerin will increase the effectiveness of treatment with induction chemotherapy and concurrent chemo-radiotherapy by reducing chemo-radio resistance through an increased oxygen pressure in tumoral tissue. The combination treatment of nitroglycerin and chemotherapy will result in longer disease-free and over-all survival in patients with locally advanced NSCLC

Detailed Description
-----------------
Nitroglycerin decreases hypoxia-induced resistance to antitumor drugs due to inhibition of Hypoxia Inducible Factor alfa (HIF-1α), it increases oxygen pressure in tumoral tissue by augmenting tumor blood flow, increases apoptosis, activation of p53, and induces cellular growth inhibition. Randomized studies showed that the addition of transdermal nitroglycerin to non small cell lung cancer (NSCLC) patients with metastasis treated with vinorelbine and cisplatin achieved a significantly better global response to treatment than conventional treatment

Official Title
-----------------
Phase II Study That Evaluates Concurrent Chemotherapy and Radiotherapy With Nitroglycerin in Patients With Locally Advanced Non-Small Cell Lung Cancer

Conditions
-----------------
Locally Advanced Non Small-Cell Lung Canger

Intervention / Treatment
-----------------
* Drug: Transdermal nitroglycerin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histopathologic diagnosis of non small-cell lung cancer Clinical stage IIIA and/or IIIB without pleural effusion ECOG functional status 0 or 1 No renal function alteration (GFR >50%) No hepatic function alteration (ALT and AST less than 2 times its normal value) Leucocytes more than 2,000/mcl Hemoglobin more than 10mg/dL Platelets more than 100,000/mcl Exclusion Criteria: Ischemic heart disease Abnormal electrocardiogram

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nytroglicerin<br> | Drug: Transdermal nitroglycerin<br>* Transdermal nitroglycerin (25mg/day) during 5 days (2 days before and 3 days after chemotherapy) at the beginning of each chemotherapy cycle for a total of 4 cycles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression, over-all survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of oxidative stress through lipid peroxidation and quantification of VEGF Toxicity from treatment with chemotherapy and concurrent chemo-radiotherapy combined with transdermal nitroglycerin |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nitroglycerin, Locally advanced non small-cell lung cancer, Vascular endothelial growth factor, Hypoxia Inducible Factor, Clinical stage IIIA and/or IIIB (without pleural effusion)