Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial.
BACKGROUND
In this study, a combination of recombinant adenoviral p53 (rAd-p53) gene therapy and intra-arterial delivery of chemotherapeutic agents for treatment of oral squamous cell carcinoma was evaluated.


METHODS
In total, 99 patients with stage III or IV oral carcinoma who had refused or were ineligible for surgery were enrolled in a randomized, placebo-controlled, double-blind, phase III clinical trial. They were randomly assigned to group I (n = 35; intra-arterial infusion of rAd-p53 plus chemotherapy), group II (n = 33; intra-arterial infusion of rAd-p53 plus placebo chemotherapy), or group III (n = 31; intra-arterial infusion of placebo rAd-p53 plus chemotherapy).


RESULTS
The median length of follow-up was 36 months (range, 3 to 86 months). During follow-up, 16 patients in group I, 20 in group II, and 22 in group III died. Group I (48.5%) had a higher complete response rate than groups II (16.7%) and III (17.2%) (P = 0.006). The rate of non-responders in group I was significantly lower than that in groups II and III (P < 0.020). A log-rank test for survival rate indicated that group I had a significantly higher survival rate than group III (P = 0.019). The survival rate of patients with stage III but not stage IV oral cancer was significantly higher in group I than in group III (P = 0.015, P = 0.200, respectively). The survival rate of patients with stage IV did not differ significantly among the three groups. Or the 99 patients, 63 patients experienced adverse events of either transient flu-like symptoms or bone marrow suppression, while 13 patients had both these conditions together. No replication-deficient virus was detected in patient serum, urine, or sputum. rAd-p53 treatment increased Bax expression in the primary tumor of 80% of patients, as shown by immunohistochemical staining.


CONCLUSIONS
Intra-arterial infusion of combined rAd-p53 and chemotherapy significantly increased the survival rate of patients with stage III but not stage IV oral cancer, compared with intra-arterial chemotherapy. Intra-arterial infusion of combined rAd-p53 and chemotherapy may represent a promising alternative treatment for oral squamous cell carcinoma.


BACKGROUND
ChiCTR-TRC-09000392 (Date of registration: 2009-05-18).
Yi
Y
Li
State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China. muzili63@163.com.
Long-Jiang
LJ
Li
Li-Juan
LJ
Wang
Zhuang
Z
Zhang
Ning
N
Gao
Chen-Yuan
CY
Liang
Yuan-Ding
YD
Huang
Bo
B
Han
D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics
D000970:Antineoplastic Agents; D011994:Recombinant Proteins