P53 MUTATIONS DO NOT PREDICT RESPONSE TO PACLITAXEL RADIATION FOR NONSMALL CELL LUNG-CARCINOMA/

BACKGROUND. Mutations in the tumor suppressor gene p53 have been assoc iated with resistance to ionizing radiation and chemotherapy. Paclitax el and concurrent radiation (paclitaxel/RT) achieve high response rate s with locally advanced nonsmall cell lung carcinoma (NSCLC). In vitro data and animal studies suggest that paclitaxel may have a unique abi lity to activate tumor eel apoptosis in the absence of wild-type p53 f unction. The authors sought to determine whether p53 mutations affect response to paclitaxel/RT in patients with locally advanced NSCLC. MET HODS. Thirty patients with Stage IIIA or IIIB NSCLC who participated i n Brown University Oncology Group protocols utilizing paclitaxel/RT ha d tumor tissue that was adequate for analysis. Mutations were detected in tumor tissue by single-strand conformation polymorphism analysis o f exons 5 through 8 of the p53 gene, and confirmed by direct sequencin g. RESULTS. Mutations in p53 were found in 12 of 30 patients (40%). Th e response rates (complete plus partial) of 75% for patients with tumo rs with p53 mutations, and 83% for patients with wild-type p53, did no t differ significantly (P = 0.70). CONCLUSIONS. p53 mutations do not p redict response of patients with NSCLC to paclitaxel/RT. This finding is in striking contrast to results with other chemotherapeutic agents and ionizing radiation. These clinical data support in vitro data and animal studies regarding the unique mechanism of the action of paclita xel. Further investigation is needed to determine the mechanism of lun g tumor cell death after paclitaxel/RT. These results suggest that pac litaxel/RT may be an active regimen for patients with other locally ad vanced neoplasms with high rates of p53 gene mutations. (C) 1996 Ameri can Cancer Society.