The AKT inhibitor perifosine in biochemically recurrent prostate cancer: A phase II California/Pittsburgh cancer consortium trial

Karen G. Chee, Jeff Longmate, David I. Quinn, Gurkamal Chatta, Jacek Pinski, Przemyslaw Twardowski, Chong-Xian Pan, Angelo Cambio, Christopher P Evans, David R Gandara, Primo N Lara

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Background: 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. Patients and Methods: 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 therapy < 9 months in duration (completed ≥ 1 year before registration) was allowed. The primary endpoint was PSA response, defined as a decrease by ≥ 50% from the pretreatment value. Treatment was comprosed of a loading dose of perifosine 900 mg orally on day 1, then 100 mg daily starting 24 hours later. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)433-437
Number of pages5
JournalClinical Genitourinary Cancer
Volume5
Issue number7
DOIs
StatePublished - Dec 2007

Keywords

  • Alkylphospholipids
  • Androgen deprivation therapy
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Oncology
  • Urology

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