Clinical Study On Safety And Short-term Efficacy Of Combination Surgery With Recombined Adenovirus P53 Intrapleural Indwelling For Non-small Cell Lung Cancer

BackgroundFor a long time, early-stage non-small cell lung cancer(NSCLC) has been treated by surgery and adjuvant chemotherapy. The lymph node metastasis and blood metastasis of NSCLC are later than those of small cell lung cancer,. so surgery for NSCLC can achieve more satisfactory therapeutic effect.But in recent years, the tumor cells have shown increasingly resistant to chemotherapy drugs such as platinum, paclitaxel, docetaxel, gemcitabine and vinorelbine. If the bloody and lymphatic metastasis of tumor cells were not found before surgery or tumor cells were left over during operation, these “early-stage” NSCLC may have poor prognosis. Therefore, it is imminent for us to find safer and more effective treatment for NSCLC.Recent studies have showed that the use of recombinant adenovirus p53(r Ad-p53) for NSCLC by intratumoral injection, arterial injection, intravenous injection and other ways can reduce the tumor volume, and clinical remission can be found in some cases. Malignant pleural effusion can be controlled by r Ad-p53 in some clinical research. r Ad-p53 combined with chemotherapy or radiotherapy for NSCLC can enhance the effect. Even r Ad-p53 can reverse the resistance to some drugs.However, we didn’t found any study on combination surgery with intrapleural r Ad-p53 indwelling for NSCLC.ObjectiveTo observe and assess the safety and efficacy of combination surgery with intrapleural r Ad-p53 indwelling for NSCLC.Methods1. NSCLC Volunteers were continuously recruited to participate in this clinical study. They were asked to sign informed consent, and got a serial number.2. A detailed case history, physical examination, laboratory tests, chest X-ray and CT scan, bronchoscopy, biopsy of lesions and other tests were got before surgery.3. According to the given serial number, volunteers were randomized into test or control group by the random numbers from SPSS 13.0.4. Cases in the test group received treatment of surgery combined with intrapleural r Ad-p53, cases in the control group were treated by only surgery.5. Adverse events in the peri-operative period were observed. Some data were recorded including laboratory test results, fever cases, adverse events, complications, operative time, bleeding, chest drainage volumes, continuous drainage time and so on.6. Periodical follow-up was carried out in all cases by calling or sending a letter. The end point times including local recurrence, distant metastasis or death were recorded.7. The intra-operative and post-operative outcomes, adverse events were statistically analyzed. Squamous cell carcinoma and adenocarcinoma progression-free survivals were analyzed respectively by Kaplan-Meier method.Results1. Laboratory parameters: there is no statistical difference of white blood cell(WBC), platelets(PLT), aspartate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(Cr) between the test group and the control group(P> 0.05).2. Peri-operative complications: there is no statistical difference of fever, atelectasis, pulmonary infection, ARDS, respiratory failure and pneumothorax between the test group and the control group(P> 0.05).3. There is no statistical difference of operative time, bleeding, pleural drainage volumes and continuous drainage time between the test group and the control group(P> 0.05).4. In quamous cell carcinoma cases, there was significant difference of one-year progression-free survival rates between the test group(85.4%) and the control group(69.3%), the average progression-free survival time of the test group(15.7 months) was longer than that of the control group(12.5 months),P<0.05. In adenocarcinoma cases, there was significant difference of one-year progression-free survival rates between the test group(84.7%) and the control group(74%), the average progression-free survival time of the test group(16.4 months) was longer than that of the control group(15.1 months),P<0.05..ConclusionCombined surgery with intrapleural r Ad-p53 indwelling is safe and effective treatment strategy for NSCLC. This treatment would not prolong operation time, not increase the amount of bleeding, not increase the chest drainage volume, and not delay drainage time. Serious adverse event and complication would be not caused by this combination treatment. Moreover, this new kind of treatment may block tumor progression in patients with NSCLC and prolong progression-free survival time.