• Maximum tolerated dose of 5-fluoro-2'-deoxycytidine (5FD) given together with tetrahydrouridine (THU) [ Designated as safety issue: Yes ]
• Toxicity of 5FD and THU [ Designated as safety issue: Yes ]
• Pharmacokinetic profile of 5FD and THU [ Designated as safety issue: No ]
• Oral bioavailability of 5FD and THU [ Designated as safety issue: No ]
• Relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase, dCMP deaminase, and other relevant enzymes [ Designated as safety issue: No ]
• Methylation status of p16 and other genes relevant to neoplasias [ Designated as safety issue: No ]

• Maximum tolerated dose of 5-fluoro-2'-deoxycytidine (5FD) given together with tetrahydrouridine (THU)
• Toxicity of 5FD and THU
• Pharmacokinetic profile of 5FD and THU
• Relative levels of mRNAs for thymidylate synthase, deoxycytidine kinase, dCMP deaminase, and other relevant enzymes
• Methylation status of p16 and other genes relevant to neoplasias

RATIONALE: Drugs used in chemotherapy, such as 5-fluoro-2'-deoxycytidine and tetrahydrouridine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of 5-fluoro-2'-deoxycytidine when given together with 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.
• Assess the pharmacokinetics of this regimen in these patients.
• Evalutate 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.

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.

• Breast Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

• Drug: 5-fluoro-2-deoxycytidine
• Drug: tetrahydrouridine
• Other: pharmacological study
• Procedure: biopsy

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor

  • Breast cancer patients have a higher priority for accrual
• Disease must be refractory to standard therapy OR no standard therapy exists

• Measurable disease allowed, but not required

  • If bidimensionally measurable disease is present, baseline measurements of ≤ 3 indicator lesions must be available within the past 4 weeks
  • No pleural effusions, ascites, or bone metastases as measurable disease
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Male or female
• Menopausal status not specified
• Life expectancy ≥ 2 months
• Creatinine ≤ 2.0 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 125,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• SGOT and SGPT ≤ 3 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent severe poorly controlled nonmalignant illness (e.g., cardiovascular, pulmonary, or central nervous system disease)

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• Recovered from prior major surgery
• At least 4 weeks since prior and no other concurrent antineoplastic therapies
• No concurrent treatment for severe infection
• No other concurrent investigational therapy