A Phase I Trial of Lometrexol Sodium and Paclitaxel Adminsitered Intravenously Every 21 Days in Conjunction With Oral Folic Acid in Patients With Solid Tumors

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II study dose of lometrexol and paclitaxel when combined with folic acid in patients with locally advanced or metastatic solid tumors.
• Determine the quantitative and qualitative toxic effects of this regimen in these patients.
• Determine the plasma concentrations of lometrexol and paclitaxel and relate their pharmacokinetics to toxicity outcome in these patients.
• Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of lometrexol and paclitaxel.

Patients receive lometrexol IV over 30-60 seconds immediately followed by paclitaxel IV over 3 hours on day 1. Patients also receive oral folic acid beginning 7 days before lometrexol/paclitaxel and continuing for 14 days. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Doses of lometrexol and paclitaxel are escalated sequentially. Cohorts of 3-6 patients receive escalating doses of lometrexol and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. Six to twelve additional patients are treated at the recommended phase II study dose (dose immediately preceding the MTD).