Topoisomerase I (Top1) Amplifications And Deletions As A Predective Marker For Chemotherapy With Topotecan In Women With Advanced Ovarian Cancer (OC)

Topoisomerase I is known as the cellular target of topotecan, a well established drug in the treatment of advanced OC. The aim of this study was to evaluate the predictive role of changes on the TOP1-gene for the efficacy of chemotherapy with topotecan in women with relapsed OC. Out of a database of 70 pt, who received treatment with topotecan for platinresistent recurrent OC between June 1996 and June 2000 on the Dep. of Oncology, Copenhagen the first twenty primary tumour samples were collected retrospectively and analysed for TOP1-changes by fluorescence in situ hybridisation (FISH). Pt were classified in 2 groups: either with clinical benefit (stable disease (SD), partial response (PR), complete response (CR)) or without clinical benefit (progressive disease (PD)) after 4 cycles of chemotherapy. Results: In 18 of the 20 tissue samples the FISH analysis was technically correct. The group with no clinical benefit contained 4 pt (22%) and a total of 14 pt (38%) had clinical benefit of topotecan treatment. One pt was reported with PR and CR, respectively. In 18 of the 20 tissue samples the FISH analysis was technically correct. The group with no clinical benefit contained 4 pt (22%)and a total of 14 pt (38%) had clinical benefit of topotecan treatment. One pt was reported with PR and CR, respectively. TOP1-amplifications were analysed in one of the 18 tumour samples, no TOP1-deletions was identified. We found that the pt with TOP1-amplification had CR after 4 cycles chemotherapy TOP1-amplification could have a predictive value for the activity of topotecan in treatment of recurrent platinresistent OC. More FISH analysis are needed to confirm this finding and the last 50 tumour tissues of our database will be analysed soon.