carboplatin and vincristine plus radiation therapy followed by adjuvant chemotherapy in treating young patients with newly diagnosed cns embryonal tumors

Conditions: Brain Tumors; Central Nervous System Tumors; Neuroblastoma

Summary: rationale: drugs used in chemotherapy, such as carboplatin and vincristine, work in 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. combining carboplatin and vincristine with radiation therapy followed by adjuvant chemotherapy may kill more tumor cells. purpose: randomized phase ii trial to study the effectiveness of combination chemotherapy plus radiation therapy followed adjuvant chemotherapy in treating young patients who have newly diagnosed high-risk cns embryonal tumors.

objectives: * determine the feasible dose and duration of carboplatin combined with craniospinal and local radiotherapy and adjuvant chemotherapy in children with newly diagnosed, high-risk cns embryonal tumors (phase i completed as of 11-25-03). * determine the feasibility of administering cyclophosphamide and vincristine with or without cisplatin after concurrent carboplatin, vincristine, and radiotherapy in these patients. * determine the overall and individual toxicity rates of this regimen in these patients. * determine the complete response rate in patients treated with this regimen. * obtain preliminary estimates of event-free survival of patients treated with this regimen. * determine the prognostic significance of enhancing tumor after completion of radiotherapy on event-free survival of these patients. outline: this is a pilot, dose-escalation study of carboplatin. (phase i completed as of 11-25-03.) within 31 days of definitive surgery, all patients receive vincristine iv weekly for 6 weeks and carboplatin iv over 15-20 minutes (after completion of vincristine infusion) 5 days a week for 6 weeks. patients undergo radiotherapy (1-4 hours after carboplatin infusion) 5 days a week for 6 weeks. cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose at which no more than 3 of 12 patients experience dose-limiting toxicity. (phase i completed as of 11-25-03.) at 6 weeks after completion of radiotherapy, patients are assigned to arm ii for adjuvant/maintenance chemotherapy. (arm i closed to accrual as of 11-25-03.) * arm i (closed to accrual as of 11-25-03): patients receive cyclophosphamide iv over 1 hour on days 0 and 1, vincristine iv on days 0 and 7, and filgrastim (g-csf) iv or subcutaneously (sc) beginning on day 2 and continuing for at least 10 days until blood counts recover. * arm ii: patients receive cyclophosphamide iv over 1 hour on days 1 and 2, vincristine iv on days 0 and 7, cisplatin iv over 6 hours on day 0, and g-csf iv or sc beginning on day 3 and continuing for at least 10 days until blood counts recover. in both arms, adjuvant/maintenance chemotherapy repeats every 4 weeks for 6 courses. patients are followed every 3 months for 8 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. projected accrual: a total of 162 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically proven high-risk cns embryonal tumors, including: * primitive neuroectodermal tumors * atypical teratoid/rhabdoid tumor * medulloblastoma * desmoplastic medulloblastoma * ependymoblastoma * medullomyoblastoma * spongioblastoma * spongioblastoma polare * primitive polar spongioblastoma * neuroepitheliomatous neoplasms * medulloepithelioma * neuroblastoma * pineoblastoma * no bone marrow involvement or bone metastases * no m4 disease * m3 disease must have evidence of tumor on spinal mri patient characteristics: age: * 3 to 21 at diagnosis performance status: * not specified life expectancy: * at least 8 weeks hematopoietic: * absolute neutrophil count greater than 1,500/mm\^3 * platelet count at least 100,000/mm\^3 (transfusion independent) * hemoglobin at least 10.0 g/dl (packed red blood cell transfusions allowed) hepatic: * bilirubin less than 1.5 mg/dl * sgot/sgpt less than 2.5 times normal renal: * creatinine less than 1.5 times upper limit of normal or * creatinine clearance or radioisotope glomerular filtration rate at least 70 ml/min prior concurrent therapy: biologic therapy: * not specified chemotherapy: * no prior chemotherapy endocrine therapy: * not specified radiotherapy: * no prior radiotherapy surgery: * prior definitive surgery allowed

Keywords: untreated childhood supratentorial primitive neuroectodermal tumor untreated childhood medulloblastoma localized unresectable neuroblastoma regional neuroblastoma stage 4s neuroblastoma