A Phase I Trial Of 2-Methoxyestradiol (2ME2), (NSC-659853) An Angiogenesis Inhibitor, In Patients With Solid Tumors

OBJECTIVES:

• Determine the maximum tolerated dose of 2-methoxyestradiol in patients with advanced solid tumors.
• Determine the side effect profile of this drug in these patients.
• Determine the pharmacokinetic profile of this drug in these patients.
• Determine the changes in positron-emission tomography scans of patients treated with this drug.
• Determine the changes in apotosis in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive oral 2-methoxyestradiol (2ME2) once on day 1 followed by 2 days of evaluation. Patients then receive oral 2ME2 every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 2ME2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.