[Effectiveness of recombinant adenovirus p53 injection on laryngeal cancer: phase I clinical trial and follow up].

Objective: To evaluate the efficacy and toxicity of recombinant adenovirus p53 injection (SBN-1) in patients with laryngeal cancer.

Methods: Twelve cases with laryngeal cancer, 11 males and 1 female, aged 59.5 +/- 12.4 years, were randomly divided into three groups of 4 patients. The patients received intratumor injection of SBN-1 at the dosage of 1 x 10(10)VP, 1 x 10(11)VP, or 1 x 10(12)VP once every other day for 2 courses of treatment with 5 times of injection as one course of treatment. Two days after the injection the patients were operated on. After the operation SBN-1 of the same doses was injected around the tumor bed. The patients were followed up for more than 3 years by correspondence and out-patient department examinations. ELISA was used to detect the serum anti-adenoviral IgG and IgM, and interleukin-2 receptor (IL-2R). Immunohistochemistry was used to examine the expression of p53 protein in the tumor tissues. Flow cytometry was used to examine the T cell subgroup. The symptoms and side effects were observed.

Results: One patient in the 10(12)VP group presented self-limited fever (38.2-38.6 degrees C) and no other abnormality was observed after the SBN-1 injection. Specific antibody to SBN-1 turned from negative to positive two or three weeks after the first injection. P53 protein expression was significantly enhanced in tumors after injection of SBN-1. The serum level of IL-2R was 750 +/- 401 pg/ml before treatment and 552 +/- 203 pg/ml after treatment. The numbers of CD3, CD4, and CD8 were 66 +/- 10, 41 +/- 15, and 32 +/- 10 respectively before the treatment and were 67 +/- 9, 43 +/- 8, and 34 +/- 16 respectively after treatment, and the CD4/CD8 ratio was 1.4 +/- 0.6 before the treatment and was 1.6 +/- 0.9 after treatment. The abnormality in SIL-2R level and the disorder of T cell subgroup were improved in 2 cases. Followed up for over 3 years showed that all cases still lived free of cancer.

Conclusion: Safe and effective on laryngeal cancer without obvious adverse events, local injection of SBN-1 is a promising treatment.