p53 mutations do not predict response to paclitaxel in metastatic nonsmallcell lung carcinoma

BACKGROUND. In vitro data and animal studies suggest that paclitaxel may ha ve a unique ability to activate tumor cell apoptosis in the absence of wild -type p53 concurrent radiation was not affected by p53 mutations in nonsmal l cell lung carcinoma (NSCLC). We sought to determine whether p53 mutations affect response to paclitaxel alone in patients with metastatic NSCLC. METHODS. Twenty-five patients with metastatic NSCLC who participated in Bro wn University Oncology Group protocols utilizing single-agent weekly paclit axel had tumor tissue that was adequate for p53 analysis. Tumor tissue was evaluated for p53 gene mutations in exons 5 through 8 by single-strand conf ormation polymorphism analysis. Mutations were confirmed by direct sequenci ng of altered mobility polymerase chain reaction products. RESULTS. Mutations in p53 were found in 8 of 25 patients (32%). The respons e rates of 75% for patients with tumors with p53 mutations and 47% for pati ents with wild-type p53 do not differ significantly (P = 0.12). The 1-year survival rates for patients with and without p53 mutation after treatment w ith weekly paclitaxel were 63% (95% confidence interval [CI], 31-100%) and 53% (95% CI, 33-86%), respectively. CONCLUSIONS. p53 mutations do not adversely affect response to paclitaxel a s a single agent in metastatic NSCLC. These results provide clinical suppor t for in vitro observations that paclitaxel can bypass mutant p53 and lead to tumor cell death by alternate pathway(s). Paclitaxel should be considere d as a component of treatment for patients with metastatic NSCLC with tumor s that have p53 mutations. (C) 2000 American Cancer Society.