The AKT inhibitor perifosine in biochemically recurrent, hormone-sensitive prostate cancer (HSPC): A phase II California Cancer Consortium trial

Chee, Karen; Lara, Primo N.; Longmate, Jeff; Twardowski, Przemyslaw; Quinn, David I.; Chatta, Gurkamal S.; Gandara, David R.

doi:10.1200/jco.2005.23.16_suppl.4642

Cited by 7 publications

(4 citation statements)

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“…42 In a total of 25 patients (with 22 evaluable for response), none had a PSA decline ≥ 50%, leading to early termination of accrual. However, a total of 5 patients (23%) did have a PSA decline of < 50%, and median PFS with perifosine was an appreciable 9.5 months.…”

Section: 0 Clinically Relevant Akt Inhibitorsmentioning

confidence: 98%

Akt inhibitors in clinical development for the treatment of cancer

Pal

Reckamp

et al. 2010

Expert Opinion on Investigational Drugs

210

187

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Importance of the field The evolution of targeted therapies is dependent upon identification of cellular moieties that can be pharmacologically modulated. As one such example, the serine-threonine kinase Akt was identified nearly two decades ago. Since then, its role in mediating multiple signaling cascades (ultimately leading to cell growth and proliferation) has since been identified. More recently, several agents have been developed that antagonize Akt – these agents are in various stages of clinical testing. Areas covered in this review Herein, we outline development of several promising Akt inhibitors, including perifosine, MK-2206, RX-0201, PBI-05204, GSK2141795, and others. What the reader will gain The reader will gain insight into the current pipeline of Akt inhibitors, and the degree to which these agents have been examined both clinically and preclinically. Take home message With an emerging pipeline of agents targeting Akt, it will be critical to decipher which amongst them holds the greatest promise. Herein, we explore this drug pipeline and provide strategies for determining the future clinical application of these agents.

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Section: 0 Clinically Relevant Akt Inhibitorsmentioning

confidence: 98%

Akt inhibitors in clinical development for the treatment of cancer

Pal

Reckamp

et al. 2010

Expert Opinion on Investigational Drugs

210

187

View full text Add to dashboard Cite

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“…27 Toxicity in this study was minimized by the altered dosing schedule which did not include repeated loading doses on day 1 of cycles beyond the first and a lowered daily maintenance dose that was given without interruption.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of perifosine in androgen independent prostate cancer

Posadas¹,

Gulley²,

Arlen³

et al. 2005

Cancer Biology & Therapy

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“…A California Cancer Consortium trial in 25 patients with biochemical recurrence following definitive therapy demonstrated biological and chemical activity, with 23% of patients having a decrease in PSA, although none were 450%. 53 A National Cancer Institute study of 19 men with metastatic AI CaP and average PSA of 180 ng/ml showed no objective or PSA responses, and four patients with PSA stabilization for 12 weeks. 54 Although perifosine is apparently relatively ineffective as monotherapy, the strong preclinical rationale combined with preclinical results showing synergism with other Akt inhibitory drugs suggest the need for more trials examining its role in an adjunctive setting.…”

Section: Perifosinementioning

confidence: 99%

Inhibition of Akt pathways in the treatment of prostate cancer

Nelson

Evans

Mack

et al. 2007

Prostate Cancer Prostatic Dis

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Akt is a serine/threonine kinase mediating multiple intracellular pathways involved in prostate cancer (CaP) biology. Increased understanding of the molecular mechanisms of Akt activation and signaling have led to the development of an increasing number of Akt inhibitors. These biologic agents demonstrate activity against a wide range of cancers in preclinical studies. Clinical studies of Akt inhibition in CaP are in progress, including agents such as celecoxib, perifosine and genistein. How best to integrate Akt inhibitors with standard CaP therapy or select patients most likely to benefit is the subject of ongoing research.

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The AKT inhibitor perifosine in biochemically recurrent, hormone-sensitive prostate cancer (HSPC): A phase II California Cancer Consortium trial

Cited by 7 publications

References 0 publications

Akt inhibitors in clinical development for the treatment of cancer

Akt inhibitors in clinical development for the treatment of cancer

A phase II study of perifosine in androgen independent prostate cancer

Inhibition of Akt pathways in the treatment of prostate cancer

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