p53 Gene Status and Response to Platinum/Paclitaxel-Based Chemotherapy in Advanced Ovarian Carcinoma
Articolo
Data di Pubblicazione:
2000
Citazione:
p53 Gene Status and Response to Platinum/Paclitaxel-Based Chemotherapy in Advanced Ovarian Carcinoma / C. Lavarino, S. Pilotti, M. Oggionni, L. Gatti, P. Perego, G. Bresciani, M. A. Pierotti, G. Scambia, G. Ferrandina, A. Fagotti, C. Mangioni, V. Lucchini, F. Vecchione, G. Bolis, G. Scarfone, F. Zunino. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 18:23(2000 Dec), pp. 3936-3945.
Abstract:
Purpose: The p53 gene plays a critical role in cellular
response to DNA damage and has been implicated in the
response to platinum compounds in ovarian carcinoma
patients. Because taxanes could induce p53-independent
apoptosis, we assessed the relevance of p53 gene status
to response in ovarian carcinoma patients receiving paclitaxel
and platinum-containing chemotherapy.
Patients and Methods: Forty-eight previously untreated
patients with advanced disease received standard
paclitaxel/platinum-based chemotherapy. In tumor
specimens collected at the time of initial surgery,
before therapy, p53 gene status and expression were
examined by single-strand conformation polymorphism,
sequence analysis, and immunohistochemical
analysis. Microsatellite instability analysis was performed
on available samples from 30 patients.
Results: Thirty-four (71%) of the 48 patients had a
clinical response. Pathologic complete remission was
documented in 13 (27%) of 48 patients. p53 mutations
were detected in 29 (60%) of 48 tumors. Among the
patients with mutant p53 tumors, 25 patients (86%)
responded to chemotherapy. Only nine (47%) of 19
patients with wild-type p53 tumors responded to the
same treatment. The overall response rate and the
complete remission rate were significantly higher
among patients with mutant p53 tumors than among
patients with wild-type p53 tumors (P 5 .008). Most of
the tested tumors not associated with complete remission
(10 of 12 tumors) were also characterized by
microsatellite instability. The complete remission rate
was higher among patients with tumors without microsatellite
instability (five of seven patients).
Conclusion: In contrast to the limited efficacy of
treatment with paclitaxel in combination with standard
platinum doses against wild-type p53 ovarian tumors,
patients with mutant p53 ovarian tumors were more
responsive to paclitaxel-based chemotherapy. The pattern
of response to chemotherapy containing paclitaxel
is different from that associated with high-dose cisplatin
therapy. Determining p53 mutational status can be
useful in predicting therapeutic response to drugs effective
in ovarian carcinoma.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
C. Lavarino, S. Pilotti, M. Oggionni, L. Gatti, P. Perego, G. Bresciani, M. A. Pierotti, G. Scambia, G. Ferrandina, A. Fagotti, C. Mangioni, V. Lucchini, F. Vecchione, G. Bolis, G. Scarfone, F. Zunino
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