Lung cancer is the leading cause of cancer deaths worldwide, 85% of which are non-small cell lung cancer. The combination of platinum-containing and paclitaxel chemotherapy is generally used to treat non-small cell lung cancer, but studies have shown that it is only 19% effective, with a median survival time of about 9-10 months. Although the use of bevacizumab has extended median survival by 2 months for patients with nonsquamous non-small cell lung cancer, increased bleeding and other toxic effects have limited the use of bevacizumab. Since the late 1990s, doxorubicin, erlotinib, and pemetrexed have been used for second-line treatment of NSCLC. doxorubicin at a dose of 75 mg/m2 can be used for the treatment of patients with progressive advanced or metastatic NSCLC with a behavioral status score of 0-2 after platinum-containing first-line therapy. two clinical trials, TAX317 and TAX320, both reported that doxorubicin may improve overall patient survival and quality of life. In a phase III clinical trial comparing the efficacy of pemetrexed and doxorubicin, median survival was similar, although pemetrexed had a better drug safety profile than doxorubicin. Erlotinib, as an epidermal growth factor receptor inhibitor, is considered an appropriate choice for third-line treatment of patients with advanced NSCLC. In addition, an in-depth comparative study of gefitinib and doxorubicin in Japanese patients found no statistical difference in overall survival between gefitinib and doxorubicin. Gefitinib is currently used to treat patients with all histological types of NSCLC in which sensitive EGFR mutations are clearly present in the tumor. This phase III trial was conducted globally in patients with stage IIIb/IV NSCLC of all histologic types who were receiving first-line chemotherapy or whose disease had progressed after first-line chemotherapy and were eligible for second-line chemotherapy, with the goal of demonstrating the benefit of ASA404 in combination with doxorubicin for overall survival in this patient population. Patients treated with bevacizumab and/or EGFR inhibitors were allowed to participate in this trial. Second-line regimens with doxorubicin showed improved overall survival compared to best supportive care and monotherapy [Hanna et al, 2004]. In contrast, ASA404 is a novel tumor-vascular cleavage agent (Tumor-VDA) that causes irreversible tumor vascular collapse, hemorrhagic necrosis in the tumor center, and heightened cell-mediated toxic response. In an ongoing trial in non-small cell lung cancer [McKeage, 2008], similar to the results of preclinical and clinical trials, ASA404 showed excellent synergistic activity with paclitaxel analogs (including doxorubicin) and an impressive lack of overlapping toxicities in their combination. Similar results were also seen in phase II clinical trials in NSCLC and ovarian cancer. ASA404 was generally well tolerated, and all ASA404-induced adverse events were irreversible CTC primary or secondary toxicity, which ended with the end of treatment. Based on these results, the combination of ASA404 with doxorubicin may be safer and more effective in prolonging patient survival. In this trial, overall survival was used as the primary trial endpoint to evaluate the efficacy of its second-line treatment in patients with NSCLC stage IIIb/IV.