title: Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer.
abstract: OBJECTIVE
  The objective of this study is to establish clinical evidence that the p53 genotype can serve as a predictive marker for response to cisplatin-based induction therapy.
  
  
  METHODS
  Patients with advanced non-small cell lung cancer who had received neoadjuvant chemotherapy in the context of a prospective phase II trial were analyzed for the p53 genotype of their tumors. Response to induction therapy was then correlated to the p53 genotype as assessed by complete direct DNA sequencing. Patients had received 3 cycles of cisplatin and etoposide, and 1 cycle of simultaneous radiochemotherapy. All 3 treatment components mediate their cytotoxic effect through induction of apoptosis, which is suggested to require an intact p53 gene. In addition, the results from a previously published hypothesis-finding study are updated to demonstrate the consistency of clinical results and summarize currently available clinical evidence.
  
  
  RESULTS
  In the phase II trial, 35 patients underwent resection after induction chemotherapy, allowing a pathohistologic response assessment. The presence of a mutant p53 genotype was highly indicative of resistance to induction chemotherapy (P < .002). The sensitivity of a mutant p53 genotype to identify nonresponders was 94% (71.3-99.9 confidence interval). A normal p53 gene was significantly associated with radical resection (P < .004) and survival advantage (P = .02).
  
  
  CONCLUSIONS
  This is the second clinical evaluation demonstrating a significant relation between p53 genotype and response to induction therapy in non-small cell lung cancer. We conclude that the p53 genotype should be evaluated as a predictive marker for response to induction therapy in prospective randomized protocols.
authors.affiliation: Division of Surgery, Medical University of Vienna, Austria. Daniela.Kandioler@meduniwien.ac.at
authors.forename: Daniela
authors.initials: D
authors.lastname: Kandioler
authors.forename: Georgios
authors.initials: G
authors.lastname: Stamatis
authors.forename: Wilfried
authors.initials: W
authors.lastname: Eberhardt
authors.forename: Sonja
authors.initials: S
authors.lastname: Kappel
authors.forename: Sabine
authors.initials: S
authors.lastname: Zöchbauer-Müller
authors.forename: Irene
authors.initials: I
authors.lastname: Kührer
authors.forename: Martina
authors.initials: M
authors.lastname: Mittlböck
authors.forename: Ronald
authors.initials: R
authors.lastname: Zwrtek
authors.forename: Clemens
authors.initials: C
authors.lastname: Aigner
authors.forename: Christoph
authors.initials: C
authors.lastname: Bichler
authors.forename: Victoria
authors.initials: V
authors.lastname: Tichy
authors.forename: Marcus
authors.initials: M
authors.lastname: Hudec
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachleitner
authors.forename: Adelheid
authors.initials: A
authors.lastname: End
authors.forename: Michael Rolf
authors.initials: MR
authors.lastname: Müller
authors.forename: Erich
authors.initials: E
authors.lastname: Roth
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005047:Etoposide; D002945:Cisplatin