A Phase I Trial of Perifosine on a Loading Dose/Maintenance Dose Schedule in Patients With Advanced Cancer

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of perifosine on a loading dose/maintenance dose schedule in patients with advanced solid tumors.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Investigate the relationship between pharmacokinetic parameters and toxicity of this drug in these patients.
• Determine the recommended starting dose for phase II trials on this drug schedule in these patients.
• Evaluate the pharmacodynamic parameters on peripheral blood lymphocytes both before and during drug administration in these patients.
• Determine any changes in the MTD with prolonged administration (3 months, 6 months) of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive a loading dose of oral perifosine 4 times a day for 4-8 doses followed by a daily maintenance dose. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating loading doses and maintenance doses of perifosine until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxic effects.