Objective:To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53(rAd-p53)combined with hyperthermia plus or not plus radiotherapy in advanced cancer.Methods:Expression of Vascular epithelial growth factor(VEGF)after intratumoral injection of rAd-p53was assayed by immunohistochemistry(IHC)imaging.Forty-four patients with advanced cancer were enrolled into this clinical study.The patients were intratumorally injected with rAd-p53(Gendicine)at a dose of 1×1012vp once a week,with a total of 4-54(mean 7.7)times.Total of 4-29(mean 8.5)times of hyperthermia was given to the patients.Among the 44 patients,30 patients were concurrently added with radiotherapy of a total dose 30-76 Gy/15-38 f/3-8 w(mean 58 Gy).Results:Before and after intratumoral injection of rAd-p53,the VEGF IHC positive cell scores were 2.80and 1.50,respectively(P=0.031).The treatment of rAd-p53 combined with hyperthermia plus or not plus radiotherapy in advanced cancer achieved CR rate of 13.60%(6/44),and PR rate of 29.6%(13/44),and thus the effective rate was 43.2%.In addition to 6 patients with CR,19 patients(19/38,50.0%)had low density area(LDA)of more than 50%area on CT image within tumor indicating tumor tissue necrosis.Conclusions:Our data indicate that rAd-p53 inhibits VEGF expression and angiogenesis,and promotes tumor necrosis and shrinkage induced by hyperthermia plus or not plus radiotherapy in advanced cancer. Objective: To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53 (rAd-p53) combined with hyperthermia plus or not plus radiotherapy in advanced cancer. Methods: Expression of Vascular epithelial growth factor (VEGF) after intratumoral injection of rAd-p53was assayed by immunohistochemistry (IHC) imaging. Forty-four patients with advanced cancer were enrolled into this clinical study. The patients were intratumorally injected with rAd-p53 (Gendicine) at a dose of 1 × 1012vp once a week, with a total of 4 -45 (mean 7.7) times. Total of 4-29 (mean 8.5) times of hyperthermia was given to the patients. Among the 44 patients, 30 patients were concurrently added with radiotherapy of a total dose of 30-76 Gy / 15-38 Results: Before and after intratumoral injection of rAd-p53, the VEGF IHC positive cell scores were 2.80 and 1.50, respectively (P = 0.031). The treatment of rAd-p53 combined with hyperthermia plus or not plus radiotherapy in advanced cancer achieved CR rate of 13.6 0% (6/44), and PR rate of 29.6% (13/44), and thus the effective rate was 43.2%. Addition to 6 patients with CR, 19 patients (19/38, 50.0%) had low density area (LDA) of more than 50% area on CT image within tumor indicating tumor tissue necrosis. Conclusions: Our data indicate that rAd-p53 inhibits VEGF expression and angiogenesis, and promoting tumor necrosis and shrinkage induced by hyperthermia plus or not plus radiotherapy in advanced cancer.