paclitaxel plus radiation therapy in treating children with newly diagnosed brain stem glioma

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. paclitaxel may make the tumor cells more sensitive to radiation therapy. purpose: phase i trial to study the effectiveness of combining paclitaxel with radiation therapy in treating children who have newly diagnosed brain stem glioma.

objectives: * determine the maximum tolerated dose of paclitaxel when combined with involved-field radiotherapy in children with newly diagnosed, diffuse, intrinsic brain stem glioma. * determine the toxicity of this regimen in these patients. * assess the antitumor activity of this regimen in these patients. outline: this is a multicenter, dose-escalation study of paclitaxel. patients receive induction therapy comprising paclitaxel intravenously (iv) over 1 hour once weekly and involved-field radiotherapy (after paclitaxel infusion) once daily, 5 days a week, for 6 weeks. beginning 6 weeks after completion of induction therapy, patients may receive maintenance therapy comprising paclitaxel iv over 1 hour once every 3 weeks for a total of 8 courses. treatment continues in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of paclitaxel 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. patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. projected accrual: a minimum of 12 patients will be accrued for this study within 12-18 months.

Eligibility criteria:
disease characteristics: * newly diagnosed, diffuse, intrinsic brain stem glioma by clinical examination and magnetic resonance imaging (mri) * histologic verification not required * intrinsic (more than 50% intra-axial) involvement of the pons, pons and medulla, pons and midbrain, or entire brain stem allowed * contiguous involvement of the thalamus or upper cervical cord allowed patient characteristics: age: * 3 to 21 at diagnosis performance status: * not specified life expectancy: * not specified hematopoietic: * absolute neutrophil count greater than 1,000/mm3 * platelet count greater than 100,000/mm3 * hemoglobin greater than 10.0 g/dl hepatic: * bilirubin less than 1.5 times normal * serum glutamic oxaloacetic transaminase (sgot) or serum glutamic-pyruvic transaminase (sgpt) less than 2.5 times normal renal: * creatinine less than 1.5 times normal other: * not pregnant or nursing * negative pregnancy test * fertile patients must use a highly effective method of contraception for female patients or barrier contraception for male patients prior concurrent therapy: biologic therapy: * not specified chemotherapy: * no other concurrent anticancer chemotherapy endocrine therapy: * concurrent corticosteroid therapy for increased intracranial pressure allowed radiotherapy: * not specified surgery: * not specified other: * no concurrent cytochrome p450-inducing anticonvulsants (e.g., phenytoin or carbamazepine) during paclitaxel therapy * other concurrent anticonvulsants (e.g., valproic acid) for pre-existing seizure disorder allowed

Keywords: untreated childhood brain stem glioma