Phase II study of oral ridaforolimus in women with recurrent or metastatic endometrial cancer Academic Article uri icon

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abstract

  • OBJECTIVE: The 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. METHODS: This phase II study evaluated the single agent tolerability and activity of oral ridaforolimus administered at a dose of 40mg for 5 consecutive days followed by a 2day break, in women with recurrent or metastatic endometrial carcinoma who had received no chemotherapy in the metastatic setting. RESULTS: 31 of 34 patients were evaluable. Three partial responses (8.8%) were observed with response duration ranging between 7.9 and 26.5months. An additional 18 patients showed disease stabilization (52.9%) for a median duration of 6.6months. Response rates were not affected by previous chemotherapy exposure. No correlation was found between response and mutation status. CONCLUSION: Oral 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.

authors

  • Tsoref, Daliah
  • Welch, Stephen
  • Lau, Susie
  • Biagi, James
  • Tonkin, Katia
  • Martin, Lee Ann
  • Ellard, Susan
  • Ghatage, Prafull
  • Elit, Laurie
  • Mackay, Helen J
  • Allo, Ghassan
  • Tsao, Ming-Sound
  • Kamel-Reid, Suzanne
  • Eisenhauer, Elizabeth A
  • Oza, Amit M

publication date

  • November 2014

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