p53 gene status and response to topotecan-containing chemotherapy in advanced ovarian carcinoma

M. Oggionni, S. Pilotti, S. Suardi, A. Ditto, C. Luoni, L. Mariani, G. Scambia, F. Fanfani, F. Zunino

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Since the p53 gene has been identified as a determinant of response to chemotherapy in ovarian carcinoma in previous studies, we investigated the significance of the p53 status in response to topotecan as second-line therapy. Methods: Twenty-eight patients with advanced ovarian carcinoma, pretreated with standard platinum/paclitaxel chemotherapy, received topotecan as single-agent second-line therapy. Tumors were investigated by molecular analysis for p53 mutations in tumor samples obtained at primary surgery (i.e. before first-line therapy). Results: Wild-type p53 tumors responsive to first-line therapy maintained substantial responsiveness to topotecan. In contrast, p53 mutation was associated with a low responsiveness to second-line therapy. Conclusions: The better outcome in relapsed patients with wild-type p53 suggests that the presence of a functional wild-type p53 confers stability of the drug-sensitive phenotype. This outcome is consistent with the clinical observation that the efficacy of topotecan in the treatment of relapsed ovarian carcinoma patients is dependent on platinum sensitivity, because platinum-sensitive tumors are expected to carry wild-type p53. Although untreated mutant p53 tumors may be responsive to first-line paclitaxel- containing therapy, it is likely that loss of p53 leads to genomic instability resulting in rapid progression to drug resistance.

Original languageEnglish
Pages (from-to)154-158
Number of pages5
JournalOncology
Volume69
Issue number2
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Chemotherapy
  • Drug resistance
  • Ovarian carcinoma
  • p53
  • Topotecan

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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