کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6183269 | 1254101 | 2014 | 6 صفحه PDF | دانلود رایگان |
- Ridaforolimus is a reasonably tolerated oral mTOR inhibitor with encouraging clinical benefit response in endometrial cancer.
- Durable disease stabilization constitutes a significant proportion of responses observed.
- Factors predictive of response are still to be elucidated.
ObjectiveThe phosphatidylinositol-3 kinase/serine-threonine kinase PI3K/AKT pathway is postulated to be central to cancer cell development. Activation of this pathway is believed to promote angiogenesis, protein translation and cell cycle progression. A large percentage of endometrial carcinomas have demonstrated mutations within this regulation pathway which result in constitutional activation. The downstream effector protein mammalian target of rapamycin (mTOR) acts as a critical checkpoint in cancer cell cycling and is a logical target for drug development. The efficacy and tolerability of the oral mTOR inhibitor ridaforolimus were evaluated in this study.MethodsThis phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40Â mg for 5 consecutive days followed by a 2Â day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting.Results31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5Â months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6Â months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status.ConclusionOral ridaforolimus was reasonably tolerated and demonstrated modest activity in women with recurrent or metastatic endometrial cancers. Potential synergy between mTOR inhibition, angiogenesis and hormonal pathways warrants ongoing evaluation.
Journal: Gynecologic Oncology - Volume 135, Issue 2, November 2014, Pages 184-189