Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as cytochlor and tetrahydrouridine, may make tumor cells more sensitive to radiation therapy.

PURPOSE: This phase I trial is studying the side effects and best dose of cytochlor when given together with tetrahydrouridine and external-beam radiation therapy in treating patients with cancer that has spread to the brain.

OBJECTIVES:

Primary

* Establish the safety and toxicity profile of cytochlor and H4U when given in combination with external-beam radiotherapy for 2 weeks after treatment with the drugs alone in the previous week.

Secondary

* Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with cytochlor and H4U.
* Perform detailed pharmacokinetic studies to determine the levels of cytochlor and its metabolites in serum and in urine in weeks 1, 2, and 3 during treatment.

OUTLINE: This is a dose-escalation study of cytochlor.

Patients receive cytochlor IV and tetrahydrouridine (H4U) IV over 5 minutes on 3 days in week 1 and on days 1-5 in weeks 2 and 3. Patients also undergo external-beam radiotherapy 5 days a week in weeks 2 and 3 initiated 3-4 hours after infusions of cytochlor and H4U. Treatment may repeat in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed monthly for 3 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of metastatic cancer to the brain by contrast-enhanced MRI or CT scan
* Eligible for whole-brain radiotherapy (WBRT)

  * Patients treated with prior surgery are eligible if WBRT is to be used post operatively
  * Not planning to be treated with stereotactic radiosurgery
* No leptomeningeal metastasis documented by contrast-enhanced MRI/CT scan or cerebrospinal fluid evaluation

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Karnofsky performance status (PS) 70-100% or ECOG PS 0-1
* Leukocytes ≥ 3,000/µL
* Absolute neutrophil count \> 1,500/µL
* Platelet count \> 100,000/µL
* Total bilirubin normal
* AST and ALT \< 2.5 times upper limit of normal
* Creatinine normal OR creatinine clearance \> 60 mL/min
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation

Exclusion criteria:

* Uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or lactating
* Alcohol dependence

PRIOR CONCURRENT THERAPY:

* No prior radiotherapy to the brain
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No other concurrent chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), or other experimental medication
* No other concurrent anticancer therapy outside the protocol

  * Systemic therapy one month before or after brain radiotherapy is allowed
* No concurrent heparin or coumadin