p53 mutations do not predict response to paclitaxel in metastatic nonsmall cell lung carcinoma.
BACKGROUND
In vitro data and animal studies suggest that paclitaxel may have a unique ability to activate tumor cell apoptosis in the absence of wild-type p53 function. The authors previously demonstrated that response to paclitaxel and concurrent radiation was not affected by p53 mutations in nonsmall 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 Brown University Oncology Group protocols utilizing single-agent weekly paclitaxel 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 conformation polymorphism analysis. Mutations were confirmed by direct sequencing of altered mobility polymerase chain reaction products.


RESULTS
Mutations in p53 were found in 8 of 25 patients (32%). The response rates of 75% for patients with tumors with p53 mutations and 47% for patients 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 with 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 as a single agent in metastatic NSCLC. These results provide clinical support for in vitro observations that paclitaxel can bypass mutant p53 and lead to tumor cell death by alternate pathway(s). Paclitaxel should be considered as a component of treatment for patients with metastatic NSCLC with tumors that have p53 mutations.
King
T C
TC
Brown University Oncology Group, Providence, Rhode Island, USA.
Akerley
W
W
Fan
A C
AC
Moore
T
T
Mangray
S
S
Hsiu Chen
M
M
Safran
H
H
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000627:therapeutic use*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel