Address of Corresponding Author

Oncology 2005;69:154-158 (DOI: 10.1159/000087839)

  Key Words

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

  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.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Dr. Franco Zunino
Istituto Nazionale Tumori
Via Venezian 1
IT-20133 Milan (Italy)
Tel. +39 02 2390267, Fax +39 02 23902692, E-Mail franco.zunino@istitutotumori.mi.it

  Article Information

Received: November 17, 2004
Accepted after revision: February 26, 2005
Published online: August 24, 2005
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 3, Number of References : 23