Study on Systemic and Airway Cytokines and Oxidative Stress in Lung Cancer Patients Undergoing Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00956852
Recruitment Status : Terminated (Poor subject recruitment)
First Posted : August 11, 2009
Last Update Posted : May 12, 2016
Information provided by (Responsible Party):
James Chung-Man HO, The University of Hong Kong

Brief Summary:
Lung cancer has remained as the top cancer killer in Hong Kong. Even for early resectable stage of lung cancer, only around 60-70% of patients can survive for 5 years after operation, mostly related to disease recurrence. Therefore there is urgent need for predictive biomarkers that can potentially help in monitoring patients for risk of disease recurrence after operation. Recent studies have suggested an important role of oxidative stress in the development of lung cancer and our preliminary data have suggested that some of the oxidative stress markers in blood could be predictive of response to systemic chemotherapy for lung cancer. Apart from potential biomarkers from blood, ongoing study has also been conducted to investigate the predictive role of biomarkers in exhaled breath condensate in lung cancer patients undergoing chemotherapy. Exhaled breath condensate can be collected simply with a disposable commercially available device that allows trapping of breath condensate via a cooling column during normal breathing for 20 minutes. Therefore this study aims at investigating the role of blood and exhaled breath condensate oxidative stress biomarkers before and after surgical lung resection for lung cancer in predicting subsequent clinical outcome, i.e., timing of disease recurrence. Recruited subjects will undergo interval sampling of blood and exhaled breath condensate, without any additional invasive interventions. The study subjects will be followed up for 5 years for subsequent disease recurrence.

Condition or disease
Lung Cancer

Detailed Description:

Lung cancer is the major cause of cancer deaths among both genders in Hong Kong. In 2005, primary lung cancer accounted for 33% and 25% of all cancer deaths in men and women respectively. On average, there are around 4,000 new cases of lung cancer each year. Non-small cell lung cancer (NSCLC) accounts for about 80% of all primary lung cancers. About 60% of cases present as advanced stages IIIB and IV disease. The currently available treatment modalities include surgery, radiotherapy and systemic chemotherapy. However, the overall prognosis remains dismal with 5-year survival rate less than 15%. Among those with early stage lung cancer, the 5-year survival rate is still suboptimal at around 60-70%. Therefore, there has been immense interest in the development of novel biomarkers to delineate the high risk group for subsequent tumour recurrence after curative lung resections. It has long been found that cellular prooxidant states promote cells to neoplastic growth, in part due to DNA damage caused by reactive oxygen species (ROS), i.e. superoxide anion and hydroxyl radical. The potential therapeutic role of antioxidants in the chemoprevention of lung cancer has therefore been brought to major clinical trials in recent years. Disappointingly, the major landmark chemoprevention trials including the Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) study and the Beta-Carotene and Retinol Efficacy Trial (CARET) have failed to demonstrate therapeutic benefits of vitamins A and E in lung cancer. Apart from the criticism about the dosages being used in the trials, these results may reflect the lack of understanding of the exact role of antioxidants in lung carcinogenesis. The simple use of general antioxidants, vitamins A and E, may not be able to target specifically the peculiar alterations in antioxidant profiles that lead to the development of lung cancer. In fact, our recent study has demonstrated specific changes in antioxidant expressions in surgically resected non-small cell lung cancer. In the resected lung cancer tissues, there were increased manganese superoxide dismutase (Mn SOD) and decreased catalase expressions at the transcriptional levels as compared with adjacent normal lung tissues. It has been hypothesized that this alteration in local antioxidant levels may result in anti-apoptosis and accumulation of genetic damages thus perpetuating carcinogenesis. However the exact clinical implications are still under investigation. Our previous case-control study on the systemic (erythrocyte) antioxidant activities in patients with NSCLC has shown an increased glutathione peroxidase (GPx), but decreased SOD activities compared with healthy controls. The erythrocyte SOD activity was associated with disease staging. In addition, our recent study on longitudinal profile of erythrocyte antioxidants during chemotherapy for advanced NSCLC has identified total glutathione as an independent predictor to treatment response, which may reflect tumour load (submitted, unpublished data).

Exhaled breath condensate (EBC) has recently emerged as a non-invasive sampling method for real-time analysis and evaluation of oxidative stress biomarkers in the lower respiratory tract airways, especially in various lung diseases including asthma, chronic obstructive pulmonary disease, and lung cancer. In particular, endothelin-1 and interleukin-6 have been found to be elevated in the EBC from patients with lung cancer. Therefore, the current study aims to evaluate the temporal changes of various oxidative stress biomarkers and cytokines in EBC and blood in patients with NSCLC who are undergoing surgical lung resections and the potential role of these parameters in predicting subsequent tumour recurrence. Also, the correlation of biomarkers in blood or EBC with lung tumour tissue will be looked into.

Study Type : Observational
Actual Enrollment : 45 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Study on Systemic and Airway Cytokines and Oxidative Stress in Patients With Non-small Cell Lung Cancer (NSCLC) Undergoing Surgical Lung Resections
Study Start Date : September 2008
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Lung cancer
Non-small cell lung cancer patients undergoing surgical lung resections

Primary Outcome Measures :
  1. Time to disease recurrence [ Time Frame: 24 months after surgery ]

Secondary Outcome Measures :
  1. Disease-free survival [ Time Frame: 24 months after surgery ]

Biospecimen Retention:   Samples Without DNA
Plasma, buffy coat, red blood cell and exhaled breath condensate samples.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with early stage NSCLC who undergo curative lung resections in the Division of Cardiothoracic Surgery, Department of Surgery, Queen Mary Hospital will be recruited.

Inclusion Criteria:

  • Histologically or cytologically confirmed early-stage non-small cell lung cancer undergoing curative surgical lung resections.
  • Life expectancy > 12 weeks.

Exclusion Criteria:

  • Respiratory failure requiring use of supplemental oxygen therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00956852

Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Sponsors and Collaborators
The University of Hong Kong
Principal Investigator: Chung-man James Ho The University of Hong Kong

Responsible Party: James Chung-Man HO, Clinical Assistant Professor, The University of Hong Kong Identifier: NCT00956852     History of Changes
Other Study ID Numbers: UW 08-249
First Posted: August 11, 2009    Key Record Dates
Last Update Posted: May 12, 2016
Last Verified: May 2016

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases