The AKT Inhibitor Perifosine in Biochemically Recurrent Prostate Cancer: A Phase II California/Pittsburgh Cancer Consortium Trial
| Autor: | Primo N. Lara, Gurkamal Chatta, Przemyslaw Twardowski, Karen G. Chee, Jacek Pinski, David R. Gandara, Chong-Xian Pan, Jeff Longmate, David I. Quinn, Angelo J. Cambio, Christopher P. Evans |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Oncology medicine.medical_specialty Phosphorylcholine Urology medicine.medical_treatment Metastasis Androgen deprivation therapy Prostate cancer chemistry.chemical_compound Internal medicine medicine Humans Protein Kinase Inhibitors Aged business.industry Prostatectomy Prostatic Neoplasms Cancer Androgen Antagonists Middle Aged medicine.disease Perifosine Radiation therapy Prostate-specific antigen chemistry Neoplasm Recurrence Local business Proto-Oncogene Proteins c-akt |
| Zdroj: | Clinical Genitourinary Cancer. 5:433-437 |
| ISSN: | 1558-7673 |
| Popis: | Perifosine is an oral alkylphospholipid that inhibits cancer cell growth through decreased Akt phosphorylation. We conducted a phase II trial of perifosine in patients with biochemically recurrent, hormone-sensitive prostate cancer.Eligible patients had histologically confirmed prostate cancer, previous prostatectomy and/or radiation therapy, and rising prostate-specific antigen (PSA) without radiographic evidence of metastasis. Previous androgen deprivation therapy9 months in duration (completedor= 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease byor= 50% from the pretreatment value. Treatment was composed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later.Of 25 patients, 24 were evaluable for response. After a median follow-up of 8 months, 5 patients (20%) had a reduction in serum PSA levels, but none met criteria for PSA response. Three patients immediately progressed with no response to therapy. Median progression-free survival was 6.64 months (range, 4.53-12.81 months). No change in the PSA doubling time (7 months) was observed before and after treatment initiation. Dose-limiting toxicities (all grade 3) included hyponatremia, arthritis, hyperuricemia, and photophobia.Although well tolerated, perifosine did not meet prespecified PSA criteria for response as a single agent in biochemically recurrent prostate cancer. However, 20% of patients had evidence of PSA reduction, suggesting modest single-agent clinical activity. The role of perifosine in combination with androgen deprivation or chemotherapy is currently under investigation. |
| Databáze: | OpenAIRE |
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