Adenovirus-mediated wild-type p53 gene transfer as a surgical adjuvant in advanced head and neck cancers.
A high incidence of locoregional failure contributes to the poor overall survival rate of around 50% for patients with squamous cell carcinoma of the head and neck (SCCHN). In vitro and in vivo preclinical work with adenovirus-mediated wild-type p53 gene transfer using the recombinant p53 adenovirus (Ad-p53) has shown its promise as a novel intervention strategy for SCCHN. These data have translated into Phase I and Phase II studies of Ad-p53 gene transfer in patients with advanced, locoregionally recurrent SCCHN. The safety and overall patient tolerance of Ad-p53 has been demonstrated. Of 15 resectable but historically noncurable patients in the surgical arm of a Phase I study, 4 patients (27%) remain free of disease, with a median follow-up time of 18.25 months. Surgical and gene transfer-related morbidities were minimal. These results provide preliminary support for the use of Ad-p53 gene transfer as a surgical adjuvant in patients with advanced SCCHN. The implications of our findings for the management of SCCHN in general are discussed.
Clayman
G L
GL
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Frank
D K
DK
Bruso
P A
PA
Goepfert
H
H
D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D016159:Tumor Suppressor Protein p53 / Q000008:administration & dosage / Q000235:genetics*
D016159:Tumor Suppressor Protein p53