• 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 ]
  
• 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 ]
  

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.
• 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 tetrahydrouridine (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 before course 1 and on the last day of study treatment for pharmacodynamic studies. During course 1, plasma is collected on days 1, 3, and 5 and urine is collected on days 1 and 3 for pharmacokinetic studies.

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

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