Perifosine plus docetaxel in patients with platinum and taxane resistant or refractory high-grade epithelial ovarian cancer

被引：73

作者：

Fu, Siqing ^{[1
,2
]}

Hennessy, Bryan T. ^{[2
,10
]}

Ng, Chaan S. ^{[3
]}

Ju, Zhenlin ^{[4
]}

Coombes, Kevin R. ^{[4
]}

Wolf, Judith K. ^{[5
]}

Sood, Anil K. ^{[5
,9
]}

Levenback, Charles F. ^{[5
]}

Coleman, Robert L. ^{[5
]}

Kavanagh, John J. ^{[5
]}

Gershenson, David M. ^{[5
]}

Markman, Maurie ^{[2
]}

Dice, Kristine ^{[2
]}

Howard, Adrienne ^{[1
]}

Li, Jane ^{[6
]}

Li, Yang ^{[6
]}

Stemke-Hale, Katherine ^{[6
]}

Dyer, Mary ^{[6
]}

Atkinson, Edward ^{[7
]}

Jackson, Ed ^{[3
]}

Kundra, Vikas ^{[3
]}

Kurzrock, Razelle ^{[1
]}

Bast, Robert C., Jr. ^{[2
,8
]}

Mills, Gordon B. ^{[6
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Med Oncol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[10] Beaumont Hosp, Dublin 9, Ireland

来源：

GYNECOLOGIC ONCOLOGY | 2012年 / 126卷 / 01期

基金：

爱尔兰科学基金会;

关键词：

Perfosine; Docetaxel; Epithelial ovarian cancer; Platinum resistanc; Taxane resistance; AKT; PHASE-II TRIAL; POSITRON-EMISSION-TOMOGRAPHY; PATHWAYS CONTRIBUTES; SIGNALING PATHWAYS; INDUCED ACTIVATION; PROTEIN-KINASE; IN-VITRO; CELL; PACLITAXEL; CARCINOMA;

D O I：

10.1016/j.ygyno.2012.04.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Objectives. On the basis of reversal of taxane resistance with ART inhibition, we initiated a phase I trial of the AKT inhibitor perifosine with docetaxel in taxane and platinum-resistant or refractory epithelial ovarian cancer. Methods. Patients with pathologically confirmed high-grade epithelial ovarian cancer (taxane resistant, n = 10; taxane refractory, n = 11) were enrolled. Peripheral blood samples and tumor biopsies were obtained and F-18-FDG-PET and DCE-MRI scans were performed for pharmacodynamic and imaging studies. Results. Patients received a total of 42 treatment cycles. No dose-limiting toxicity was observed. The median progression-free survival and overall survival were 1.9 months and 4.5 months, respectively. One patient with a PTEN mutation achieved a partial remission (PR) for 7.5 months, and another patient with a PIK3CA mutation had stable disease (SD) for 4 months. Two other patients without apparent PI3K pathway aberrations achieved SD. Two patients with KRAS mutations demonstrated rapid progression. Decreased phosphorylated S6 correlated with F-18-FDG-PET responses. Conclusions. Patients tolerated perifosine 150 mg PO daily plus docetaxel at 75 mg/m(2) every 4 weeks. Further clinical evaluation of effects of perifosine with docetaxel on biological markers and efficacy in patients with ovarian cancer with defined PI3K pathway mutational status is warranted. (c) 2012 Elsevier Inc. All rights reserved.

引用

页码：47 / 53

页数：7

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