Ovarian Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Ovarian Cancer, including details on symptoms, causes, treatment, information. | ||||||||
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p53 Gene status and response to topotecan-containing chemotherapy in advanced ovarian carcinoma.Oggionni M, Pilotti S, Suardi S, Ditto A, Luoni C, Mariani L, Scambia G, Fanfani F, Zunino F Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italia. 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. Published 23 September 2005 in Oncology, 69(2): 154-8.
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