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Wednesday 25 April 2007

Phenoxodiol-Topotecan Co-Administration Exhibit Significant Anti-Tumor Activity Without Major Adverse Side Effects.

By: Alvero AB, Brown D, Montagna M, Matthews M, Mor G.

Cancer Biol Ther 2007 Apr;6(4): [Epub ahead of print]

Objective: We previously showed that Phenoxodiol is able to sensitize epithelial ovarian cancer cells to Paclitaxel, Carboplatin, Gemcitabine, and Docetaxel. The aim of this study was to determine the value of Phenoxodiol-Topotecan coadministration. Methods: Nine epithelial ovarian cancer cell lines isolated from ascites or ovarian tissue were treated with increasing concentrations of Topotecan (5-500 ng/ml) with or without Phenoxodiol pretreatment (10 mug/ml) for 24 h and cell viability was measured using CellTiter 96((R)) AQueous One Solution Cell Proliferation Assay. The effect of Phenoxodiol-Topotecan combination therapy in vivo was determined using the topotecan resistant A2780 mouse xenograft model. Results: In vitro, pretreatment with Phenoxodiol lowers tshe topotecan IC(50) from >500 ng/ml to 2.5-100 ng/ml in five out of nine cell lines tested. Results from animal experiments confirmed the advantage of Phenoxodiol-Topotecan combination therapy over monotherapy controls. Median tumour kinetics from animals receiving Phenoxodiol-Topotecan in combination was significantly slower compared to those animals receiving the respective monotherapies. In addition, co-administration with Phenoxodiol reversed Topotecan-induced myelosuppression. Conclusion: Phenoxodiol-Topotecan combination therapy allows the administration of both agents at lower doses while retaining significant anti-tumor activity compared to monotherapy. These findings suggest that the Phenoxodiol-Topotecan combination may represent an alternative treatment modality for the management of ovarian cancer and justifies further investigation in the clinical setting.

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