BMC Cancer 2009, 9:421 http://www.biomedcentral.com/1471-2407/9/421 Ar ea under the cur ve BV1 BV2 BV3 0.339 0.724 0.817 (aeRFBvseitagVci mu2lea)irbav,etelaeiron3-bndoepocfoeyfrcraeletsitn3phgoe(nBcshsVtea3rt)atocottfehrtehisretaripcaysp(ybRycOypcClales)m1cua(rBVvVeEs1G)fF,ocrlyeacvnleeles2arly Receiver-operating characteristics (ROC) curves for an early estimation of response to therapy by plasma VEGF levels available before the start of therapy cycle 1 (BV1), cycle 2 (BV2), and cycle 3 (BV3). was observed in responders while in non-responders, there was an increase in VEGF levels, an observation sim- ilar to ours. In another study, no difference in serum VEGF levels was observed from samples taken before first cycle after 24 hours and 48 hours of cisplatin-based chemother- apy in NSCLC patients [13]. Similarly, in a study of advanced NSCLC patients on cisplatin and gemcitabine regimen, no difference in serum VEGF levels was observed before first and after 3rd cycles of chemotherapy [14]. In a phase II study of stage III NSCLC patients on concurrent chemoradiation given with celecoxib (COX-2 inhibitor), serum VEGF levels did not predict response [15]. Circulat- ing VEGF levels were also used for predicting response in NSCLC patients on second-line chemotherapy. Yoshim- oto et al. [16] measured serum VEGF levels before and after second-line gefitinib therapy in 52 NSCLC patients and observed no significant change after the treatment, even in responders. In a multi-centric phase II study of 58 NSCLC patients on second-line treatment, a decrease in serum VEGF levels after two cycles was significantly asso- ciated with clinical response [17]. Circulating VEGF levels have also been monitored during the course of chemo- therapy in SCLC patients. Tas et al. [18] measured VEGF levels before first cycle and after 2nd cycle of chemotherapy in 34 SCLC patients. There was no significant difference in serum VEGF levels before after cytotoxic therapy (18). In another study, a non-significant increase in serum VEGF levels was observed in both responders and non-respond- ers after 3rd cycle of chemotherapy in a group of 39 SCLC patients [19]. Recently, a number of studies have been done where pre- treatment VEGF levels were correlated with progression- free survival (PFS), overall survival (OS), and response to treatment in lung cancer patients being treated with anti- angiogenesis drugs alone or in combination with conven- tional chemotherapy. In a recent study by Hanrahan et al [20] pre-treatment VEGF levels were correlated with PFS in three randomized phase II trials in advanced NSCLC. They found that, in NSCLC patients on second/third line treatment, those having low baseline plasma VEGF level had a significantly superior PFS when treated with vande- tanib (VEGF receptor/EGFR receptor inhibitor) mono- therapy compared with gefitinib monotherapy. Similarly, in a Japanese study, baseline plasma VEGF levels were lower in patients who experienced clinical benefit after vandetanib treatment [21]. Both studies suggest that determining pre-treatment circulating VEGF levels may have the potential to identify patients who would derive benefit from first-line targeted therapy with vandetanib. In contrast to this, in the Eastern Cooperative Oncology Group 4599 trial of carboplatin-paclitaxel with or without bevacizumab in NSCLC, high baseline plasma VEGF were associated with a greater response rate with the use of bev- acizumab but not with improved survival [22]. We also observed a greater response rate in patients with higher pre-treatment plasma VEGF levels in NSCLC patients treated with platinum-based chemotherapy. There are few reports available correlating pre-treatment VEGF levels with response to therapy and overall survival of patients treated by conventional chemotherapy. In a study on 52 advanced stage NSCLC patients treated with cisplatin plus vinorelbine, no correlation between pre- treatment serum VEGF levels and response to therapy was observed [23]. This observation is similar to ours on NSCLC patients treated with platinum doublets. In con- trast, Laack et al [24] reported a significant correlation between pre-treatment serum VEGF levels and response to therapy in metastatic NSCLC patients treated in a rand- omized phase III trial comparing gemcitabine plus vinor- elbine (GV) and gemcitabine plus vinorelbine plus cisplatin (GVP). Data regarding association of VEGF levels with survival in NSCLC is conflicting, some studies show- ing a correlation [25-27] whereas other not being able to do so [15,28,29]. In the present study, we observed a significant difference in overall survival time between patients with remission as compared to patients with no change or progression. Page 9 of 12 (page number not for citation purposes)