Xiaofan Li1, Shaowen Xiao1, Yongheng Li1, Shanwen Zhang1. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Departure of Radiotherapy, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Abstract
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-p53 was 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 1×10(12) vp 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 2.80 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 13.60% (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-p53 was 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 1×10(12) vp 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 2.80 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 13.60% (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.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Jürgen Kuball; Shu Fen Wen; Joachim Leissner; Derek Atkins; Patricia Meinhardt; Erlinda Quijano; Heidrun Engler; Beth Hutchins; Daniel C Maneval; Michael J Grace; Mary Ann Fritz; Stefan Störkel; Joachim W Thüroff; Christoph Huber; Martin Schuler Journal: J Clin Oncol Date: 2002-02-15 Impact factor: 44.544
Authors: Stephen G Swisher; Jack A Roth; Ritsuko Komaki; Jian Gu; J Jack Lee; Marshall Hicks; Jae Y Ro; Waun K Hong; James A Merritt; Kamaran Ahrar; N Edward Atkinson; Arlene M Correa; Marcelo Dolormente; Linda Dreiling; Adel K El-Naggar; Frank Fossella; Rhodette Francisco; Bonnie Glisson; Susan Grammer; Roy Herbst; Armando Huaringa; Bonnie Kemp; Fadlo R Khuri; Jonathan M Kurie; Zhongxio Liao; Timothy J McDonnell; Rudolfo Morice; Frank Morello; Reginald Munden; Vassiliki Papadimitrakopoulou; Katherine M W Pisters; Joe B Putnam; Arcenio J Sarabia; Thomas Shelton; Craig Stevens; Daniel M Shin; William R Smythe; Ara A Vaporciyan; Garrett L Walsh; Min Yin Journal: Clin Cancer Res Date: 2003-01 Impact factor: 12.531
Authors: G L Clayman; A K el-Naggar; S M Lippman; Y C Henderson; M Frederick; J A Merritt; L A Zumstein; T M Timmons; T J Liu; L Ginsberg; J A Roth; W K Hong; P Bruso; H Goepfert Journal: J Clin Oncol Date: 1998-06 Impact factor: 44.544