title: p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma.
abstract: BACKGROUND
  Mutations in the tumor suppressor gene p53 have been associated with resistance to ionizing radiation and chemotherapy. Paclitaxel and concurrent radiation (paclitaxel/RT) achieve high response rates with locally advanced nonsmall cell lung carcinoma (NSCLC). 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 sought to determine whether p53 mutations affect response to paclitaxel/RT in patients with locally advanced NSCLC.
  
  
  METHODS
  Thirty patients with Stage IIIA or IIIB NSCLC who participated in Brown University Oncology Group protocols utilizing paclitaxel/RT had tumor tissue that was adequate for analysis. Mutations were detected in tumor tissue by single-strand conformation polymorphism analysis of exons 5 through 8 of the p53 gene, and confirmed by direct sequencing.
  
  
  RESULTS
  Mutations in p53 were found in 12 of 30 patients (40%). The response rates (complete plus partial) of 75% for patients with tumors with p53 mutations, and 83% for patients with wild-type p53, did not differ significantly (P = 0.70).
  
  
  CONCLUSIONS
  p53 mutations do not predict 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 paclitaxel. Further investigation is needed to determine the mechanism of lung tumor cell death after paclitaxel/RT. These results suggest that paclitaxel/RT may be an active regimen for patients with other locally advanced neoplasms with high rates of p53 gene mutations.
authors.affiliation: Department of Medicine, Brown University, Miriam Hospital, Providence, Rhode Island 02906, USA.
authors.forename: H
authors.initials: H
authors.lastname: Safran
authors.forename: T
authors.initials: T
authors.lastname: King
authors.forename: H
authors.initials: H
authors.lastname: Choy
authors.forename: A
authors.initials: A
authors.lastname: Gollerkeri
authors.forename: H
authors.initials: H
authors.lastname: Kwakwa
authors.forename: F
authors.initials: F
authors.lastname: Lopez
authors.forename: B
authors.initials: B
authors.lastname: Cole
authors.forename: J
authors.initials: J
authors.lastname: Myers
authors.forename: J
authors.initials: J
authors.lastname: Tarpey
authors.forename: A
authors.initials: A
authors.lastname: Rosmarin
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D005091:Exons / Q000235:genetics; D005260:Female; D005544:Forecasting; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000627:therapeutic use*; D018807:Polymorphism, Single-Stranded Conformational; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012074:Remission Induction; D017422:Sequence Analysis, DNA
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel