temozolomide and vinorelbine in treating patients with recurrent brain metastases

Conditions: Metastatic Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase i/ii trial to study the effectiveness of temozolomide and vinorelbine in treating patients who have recurrent brain metastases.

objectives: * determine the maximum tolerated dose of vinorelbine when administered in combination with temozolomide in patients with recurrent brain metastases (phase i accrual completed). * determine the safety and feasibility of this treatment regimen in these patients. * determine the efficacy of this treatment regimen, in terms of objective radiographic response and overall and progression-free survival, in these patients. outline: this is a dose-escalation study of vinorelbine. patients receive vinorelbine iv over 5-10 minutes on days 1 and 8 and oral temozolomide once daily on days 1-7 and 15-21. courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity. once the mtd is determined, an additional 20-35 patients will be treated at that dose level. patients are followed every 3-4 months. projected accrual: a minimum of 3 patients will be accrued for the phase i portion of this study and 20-35 patients will be accrued for the phase ii portion of this study within 2 years.

Eligibility criteria:
inclusion criterial: * age \> or = 18 years. * karnofsky performance score \> or = 60. * histopathologic confirmation of the diagnosis of a solid tumor malignancy. the brain metastasis diagnosis per se does not have to be pathologically confirmed if the clinical and neuro radiographic picture is typical. * mri (or ct if the patient cannot undergo mri) evidence of evaluable disease in the brain. * absolute neutrophil count \> or = 1,500/mm³. platelet count \> or = 100,000/mm³. * hemoglobin \> or = 10 g/dl. * bun and serum creatinine both \< 1.5 times upper limit of normal. * total and direct bilirubin both \< 1.5 times upper limit of normal. * sgot and sgpt both \< or = 3 times upper limit of normal. * alkaline phosphatase \< or = 2 times upper limit of normal. * at least two weeks must have elapsed from brain biopsy, craniotomy, or other surgery. * life expectancy \> or = 8 weeks. * patient or their legal guardian or legal next-of-kin must provide written informed consent prior to patient's registration on study. * at least four weeks must have elapsed from previous external beam radiation therapy, or eight weeks from stereotactic radiosurgery. * patients treated with radiosurgery should have evidence of progression at a distant site in the brain, or confirmation of tumor progression by biopsy or pet scan. exclusion criteria: * previous treatment with temozolomide, dacarbazine or vinorelbine. * patients who have not recovered from all acute toxicities of prior therapies. * patients with evidence of leptomeningeal metastases or primary dural metastases. * patients who are poor medical risks because of nonmalignant systemic disease, as well as those with acute infection requiring treatment with intravenous antibiotics. * patients whose psychiatric condition would, in the judgment of the principal investigator, make it unlikely that they could adhere to the requirements of the protocol.

Keywords: tumors metastatic to brain