Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer.
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.
Kandioler
Daniela
D
Division of Surgery, Medical University of Vienna, Austria. Daniela.Kandioler@meduniwien.ac.at
Stamatis
Georgios
G
Eberhardt
Wilfried
W
Kappel
Sonja
S
Zöchbauer-Müller
Sabine
S
Kührer
Irene
I
Mittlböck
Martina
M
Zwrtek
Ronald
R
Aigner
Clemens
C
Bichler
Christoph
C
Tichy
Victoria
V
Hudec
Marcus
M
Bachleitner
Thomas
T
End
Adelheid
A
Müller
Michael Rolf
MR
Roth
Erich
E
Klepetko
Walter
W
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
D014408:Biomarkers, Tumor; D005047:Etoposide; D002945:Cisplatin