cytochlor, tetrahydrouridine, and external-beam radiation therapy in treating patients with cancer that has spread to the brain

Conditions: Brain and Central Nervous System Tumors

Summary: 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

Keywords: adult tumors metastatic to brain