Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma.
OBJECTIVE
To centrally assess the safety, efficacy, and 6-year follow-up of recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC).


METHODS
A randomized controlled clinical study on rAd-p53 combined with RT in 42 patients with NPC was compared with a control group of 40 patients with NPC treated with RT alone. In the group receiving rAd-p53 combined with RT, rAd-p53 was intratumorally injected once a week for 8 weeks. Concurrent RT (70 Gy in 35 fractions) was given to the nasopharyngeal tumor and neck lymph node. Patients and tumors were monitored for adverse events and responses.


RESULTS
rAd-p53-specific p53 mRNA was detected in postinjection of rAd-p53 biopsies from 16 (94.1%) of 17 patients. Upregulation of p21/WAF1 and Bax and downregulation of vascular endothelial growth factor were observed in postinjection tumor biopsy. Complete response rate in the group receiving rAd-p53 combined with RT was observed at 2.73 times that of the group receiving RT alone (66.7% v 24.4%). Six-year follow-up data showed that rAd-p53 significantly increased the 5-year locoregional tumor control rate by 25.3% for patients with NPC treated with irradiation (P = .002). The 5-year overall survival rate and 5-year disease-free survival rate of the group receiving rAd-p53 combined with RT were 7.5% (P = .34) and 11.7% (P = .21) higher than those of the group receiving RT alone. No dose-limiting toxicity or adverse events appeared, except for transient fever after rAd-p53 administration.


CONCLUSIONS
In patients with NPC, rAd-p53 was safe and biologically active. Our results indicated that rAd-p53 improves radiotherapeutic tumor control and survival rate in patients with NPC.
Pan
Jian-ji
JJ
Department of Radiotherapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Haidian District, Beijing, People's Republic of China.
Zhang
Shan-wen
SW
Chen
Chuan-beng
CB
Xiao
Shao-wen
SW
Sun
Yan
Y
Liu
Chang-qin
CQ
Su
Xing
X
Li
Dong-ming
DM
Xu
Gang
G
Xu
Bo
B
Lu
You-yong
YY
D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger