Surgery combined with adenoviral p53 gene therapy for treatment of non-small cell lung cancer: a phase II study.

Objective: To assess the efficacy of radical surgery combined with recombinant adenoviral human p53 (rAd-p53) gene therapy in treatment of resectable non-small cell lung cancer.

Method: A total of 163 patients with resectable NSCLC meeting the inclusion criteria were randomly assigned to two groups: radical surgery alone (S) and radical surgery plus surgical wound surface injection of 2 x 1012 rAd-p53 units (SP). All patients were followed up for at least 3 years for efficacy and safety. Study endpoints were loco-regional recurrence or distant metastasis (Rec-Met) rate as primary endpoints, and progression free survival (PFS), overall survival (OS) and safety assessments as secondary endpoints.

Results: Recurrence or metastasis (Rec/Met) after surgery were 24/82 (29.27%) in SP group and 37/81 (45.68%) in S group. The difference in the Rec/Met rate was statistically significant (p = 0.0304) by chi-square test. The hazard ratios after adjusting of age and disease stage (S vs. SP) of PFS and OS are 1.772 (95% CI, 1.102 to 2.848) and 2.047 (95% CI, 1.109 to 3.377), respectively. The 3 years PFS and OS for SP vs. S were 71.9% vs. 46.9%, and 88.4% vs. 67.0%, respectively. Differences in PFS and OS between two treatment groups were significant with the p values of 0.0165 and 0.0191, respectively, using Log-Rank test.

Conclusions: The wound surface injection of rAd-p53 showed efficacious effects in preventing recurrence or metastasis and improving PFS and OS after a radical surgery in patients with NSCLC.