Radiation Therapy Combined With Chemotherapy in Treating Patients With Anaplastic Astrocytoma or Mixed Gliomas
Condition: Brain and Central Nervous System Tumors
MeSH terms: Astrocytoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: BCNU 80mg/m2; TMZ 200mg/m2; radiation therapy; CCNU; BCNU 150mg/m2; BCNU 200mg/m2; TMZ 150mg/m2 six 6-week cycles; TMZ 150mg/m2 six 8-week cycles
Intervention description: BCNU 80 mg/m2 will be administered as an intravenous infusion on days 1, 2, and 3 of the first week of radiotherapy and on days 56, 57, and 58, then every eight weeks for four more cycles for a total of 6 cycles (maximum BCNU dose 1440 mg/m2).; 200 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat every 28 days for a total of 12 cycles.; 1.8 Gy fractions (to isocenter), 1 fraction per day, 5 days per week to a dose of 59.4 Gy in 33 fractions.; CCNU at 130 mg/m2 orally every 8 weeks for a total of 6 cycles. Administered on day 1 of the first week of radiotherapy and on day 56, then administered every 8 weeks for four more cycles for a total of 6 cycles.; BCNU 150 mg/m2 will be administered as an intravenous infusion on day 5 of radiotherapy, and it will be repeated every eight weeks for a total of six cycles (maximum total BCNU dose 900 mg/m2).; BCNU 200 mg/m2 will be administered as an intravenous infusion on day 1 of radiotherapy and will be repeated every six weeks for a total of 6 cycles (maximum BCNU dose 1200 mg/m2).; 150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 6-week cycles; 150 mg/m2 orally on days 1-5 of the first week of radiotherapy. Repeat for a total of six 8-week cycles
Intervention MeSH terms: Carmustine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase I (sequential) followed by phase III (parallel)
Masking: None (Open Label)
Enrollment: 230.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: adult anaplastic astrocytoma; adult mixed glioma

Summary:

      RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in
      chemotherapy, such as temozolomide, carmustine, and lomustine, use different ways to stop
      tumor cells from dividing so they stop growing or die. Combining radiation therapy with
      chemotherapy may kill more tumor cells.

      PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to
      see how well they work compared to radiation therapy and carmustine or lomustine in treating
      patients with anaplastic astrocytoma or mixed gliomas.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically proven unifocal anaplastic astrocytoma or mixed gliomas, including the
             following:

               -  Anaplastic astrocytoma

               -  Mixed oligodendroglial/astrocytic tumors

                    -  Oligodendroglial component must be no greater than 25%

          -  No vascular proliferation and necrosis

          -  Increased cellularity, pleomorphism, and nuclear atypia allowed

          -  No tumor predominantly located in the posterior fossa (i.e., brainstem or cerebellum)

          -  Patients with prior biopsy proven low grade astrocytoma who now have anaplastic
             astrocytoma and have had no prior radiotherapy or chemotherapy also eligible

          -  Study therapy must begin within 6 weeks of diagnosis

          -  No spinal cord tumors, spinal drop metastases, or metastases to noncontiguous meninges

               -  Pathologic evidence of local meningeal infiltration by underlying tumor allowed

        PATIENT CHARACTERISTICS:

        Age:

          -  18 and over

        Performance status:

          -  Karnofsky 60-100%

        Life expectancy:

          -  At least 1 year

        Hematopoietic:

          -  Hemoglobin at least 10 g/dL

          -  Absolute neutrophil count at least 1,500/mm^3

          -  Platelet count at least 150,000/mm^3

        Hepatic:

          -  Bilirubin less than 2 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) less than 2 times ULN

          -  Alkaline phosphatase less than 2 times ULN

        Renal:

          -  Blood urea nitrogen no greater than 25 mg/dL

          -  Creatinine less than 1.5 times normal

        Pulmonary:

          -  No pre-existing lung disease that, in the investigator's opinion, would preclude
             administration of carmustine or lomustine or completion of therapy

        Other:

          -  No other major medical illness or psychiatric impairment that would preclude study
             compliance

          -  No other malignancy within the past 5 years except nonmelanomatous skin cancer or
             carcinoma in situ of the cervix

          -  No known hypersensitivity to 1 of the components of carmustine, lomustine,
             temozolomide, dacarbazine, or any other nitrosourea

          -  No active infection

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

        Biologic therapy:

          -  No prior biologic therapy

        Chemotherapy:

          -  See Disease Characteristics

          -  No prior chemotherapy

        Endocrine therapy:

          -  Not specified

        Radiotherapy:

          -  See Disease Characteristics

          -  No prior radiotherapy to brain or head and neck

        Surgery:

          -  Not specified

        Other:

          -  No other concurrent anticancer treatment for anaplastic astrocytoma until a recurrence
             is detected