5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

- Determine the maximum tolerated dose of 5-fluoro-2'-deoxycytidine when given together
with tetrahydrouridine in patients with advanced solid tumors.

- Determine the toxicity of this regimen in these patients.

- Obtain preliminary evidence of antitumor activity of this regimen in these patients.

- Assess the pharmacokinetics of this regimen in these patients.

- Evaluate the oral bioavailability of this regimen in these patients.

- Determine the relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase,
dCMP deaminase, and other relevant enzymes in patients treated with this regimen.

- Determine the methylation status of p16 and other genes relevant to neoplasias.

OUTLINE: This is a multicenter, dose-escalation study of 5-fluoro-2'-deoxycytidine (5FD).

Patients receive a single dose of oral tetrahydrouridine (THU) and oral 5FD on day 1
followed by THU IV over 3 hours and 5FD IV over 3 hours on days 2-5 and 8-12* in course 1.
Beginning in course 2 and all subsequent courses, patients receive THU IV over 3 hours and
5FD IV over 3 hours on days 1-5 and 8-12. Treatment repeats every 28 days in the absence of
unacceptable toxicity or disease progression.

NOTE: *Patients receive 5FD orally on day 8 and then IV over 3 hours on days 9-12 of course
1.

Cohorts of 3-6 patients receive escalating doses of 5FD 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.

Blood and biopsy samples are collected at baseline and periodically during study for
pharmacodynamic studies. Plasma and urine samples are collected periodically during study
for pharmacokinetic studies.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.