Investigational New Drugs

, Volume 24, Issue 5, pp 435–439

A phase II study of perifosine (D-21226) in patients with previously untreated metastatic or locally advanced soft tissue sarcoma: A National Cancer Institute of Canada Clinical Trials Group trial

  • M. Knowling
  • M. Blackstein
  • R. Tozer
  • V. Bramwell
  • J. Dancey
  • N. Dore
  • S. Matthews
  • E. Eisenhauer
Phase II Studies

DOI: 10.1007/s10637-006-6406-7

Cite this article as:
Knowling, M., Blackstein, M., Tozer, R. et al. Invest New Drugs (2006) 24: 435. doi:10.1007/s10637-006-6406-7

Summary

Background/Patients and methods: 16 adult patients with untreated measurable locally advanced or metastatic inoperable soft tissue sarcoma were treated with oral perifosine, a synthetic alkylphospholipid, believed to inhibit MAP kinase (MAP-K), protein kinase C (PKC), Akt and other regulatory proteins. Perifosine was administered orally in cycles for 21 days out of 28. Loading doses were given day 1 each cycle (900 mg cycle 1, 300 mg cycle 2+) and 150 mg daily was given days 2–21 of each cycle. Cycles were repeated until disease progression, unacceptable toxicity or patient refusal. Results: Seventeen patients were enrolled; 16 and 15 were evaluable for toxicity and response, respectively. A total of 30 cycles of perifosine were administered. Most toxic effects were grade 1 or 2 and commonly included nausea, vomiting, diarrhea, and fatigue (≥40%). Hematologic toxicity was generally mild. There were no significant biochemical abnormalities due to the drug reported. There were 4 serious adverse events (SAE)—none of which was related to perifosine. No objective responses were seen; 4 patients had stable disease for 1.3 to 8.2 months and the remainder of the patients had progressive disease.Conclusions: Perifosine when given according to this dosing schedule does not show evidence of activity in a mixed population of adult soft tissue sarcoma patients.

Keywords

Acetylphospholipid Advanced soft tissue sarcoma Perifosine Phase II Protein kinase C MAP kinase SAPK/JNK pathway Akt 

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • M. Knowling
    • 1
  • M. Blackstein
    • 2
  • R. Tozer
    • 3
  • V. Bramwell
    • 4
  • J. Dancey
    • 5
  • N. Dore
    • 6
  • S. Matthews
    • 6
  • E. Eisenhauer
    • 6
  1. 1.British Columbia Cancer AgencyVancouver
  2. 2.Mount Sinai HospitalToronto
  3. 3.Juravinski Cancer CentreHamilton
  4. 4.Tom Baker Cancer CentreCalgary
  5. 5.CTEP, NCI USBethesda
  6. 6.NCIC Clinical Trials GroupKingston

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