Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects.

Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects. Research Abstract Details 

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Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects. Abstract Text:

Ayesha B Alvero,David Brown,Michele Montagna,Marissa Matthews,Gil Mor,Ayesha B Alvero,David Brown,Michele Montagna,Marissa Matthews,Gil Mor,

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 microg/ml) for 24 h and cell viability was measured using CellTiter 96 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 the topotecan IC50 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.

Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects. Publishing Authors By Initials

AB Alvero,D Brown,M Montagna,M Matthews,G Mor,AB Alvero,D Brown,M Montagna,M Matthews,G Mor,

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Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer biology & therapy

VOLUME: 6

Page Numbers: 612-7

Journal Abbreviation: Cancer Biol. Ther.

ISSN: 1538-4047

DAY: 16

MONTH: Apr

YEAR: 2007

Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects. Information

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LANGUAGE: eng

NlmUniqueID: 101137842

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Grant and Affiliation Information for Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity without major adverse side effects.

AFFILIATION: Department of Obstetrics & Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Country: United States

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MEDLINETA: Cancer Biol Ther

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