[Evaluation of Functional p53 Biomarker Profiles Predicts Efficacy of Adenoviral p53 Gene Therapy (Advexin) in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN)]
This is the ASGT abstract:
>>[412] Evaluation of Functional p53 Biomarker Profiles Predicts Efficacy of Adenoviral p53 Gene Therapy (Advexin) in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN)
J. J. Nemunaitis, R. E. Sobol, G. Clayman, J. Hamm, W. Goodwin, Advexin Head and Neck Cancer Study Group Mary Crowley Cancer Research Centers, Dallas, TX; Introgen Therapeutics, Houston, TX; MD Anderson Cancer Center, Houston, TX; Norton Healthcare, Louisville, KY; Sylvester Comprehensive Cancer Center, Miami, FL; Baylor Sammons Cancer Center, Dallas, TX; Texas Oncology, P.A., Dallas, TX
Abnormalities of the p53 tumor suppressor gene are associated with the development and progression of malignancies. Abnormal expression of p53 is a negative prognostic factor in SCCHN. We investigated the application of p53 biomarker profile characterization to predict efficacy of Advexin in patients with recurrent SCCHN. Advexin was administered by local intratumoral injection in two randomized controlled, pivotal multicenter trials. Trial T201 involving 112 patients with different Advexin treatment schedules and trial T301 with 123 patients comparing efficacy and safety of a fixed Advexin schedule against methotrexate. All patients had histologically confirmed recurrent SCCHN and were previously treated with a minimum of standard radiation (5,000 cGy). Tumor p53 biomarker profiles were determined by p53 gene sequence analyses to detect mutations in the DNA binding domain and by p53 protein levels detected by immunohistochemistry (high level > 50% and low level <50% positive nuclear staining). Abnormal p53 detected by immunohistochemistry was a molecular predictive biomarker associated with statistically significant increases in tumor response and survival in Advexin phase 2 trials. The median survival of patients with the abnormal p53 biomarker was 11.6 months compared to only 3.5 months in patients with normal p53 tumors (p=0.0007; log-rank test). Data analyses from the T301 trial are in progress and will also be presented. In conclusion, p53 biomarkers may identify advanced SCCHN patients most likely to benefit from Advexin therapy.<<
Cheers, Tuck |
