Observation or Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Low-Grade Glioma
Observation or Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Low-Grade Glioma
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in
 chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
 die. It is not yet known whether radiation therapy combined with chemotherapy is more
 effective than radiation therapy alone in treating patients with low-grade glioma.

 PURPOSE: Phase II/III trial to evaluate observation and to compare the effectiveness of
 radiation therapy with or without combination chemotherapy in treating patients with
 low-grade glioma.
OBJECTIVES:

 -  Identify the overall survival of low-risk adult patients with supratentorial low-grade
 glioma who are observed postoperatively.

 -  Compare the overall survival of high-risk adult patients with supratentorial low-grade
 glioma who receive postoperative external beam radiotherapy with or without
 procarbazine, lomustine, and vincristine (PCV) chemotherapy.

 -  Compare the toxic effects of postoperative radiotherapy with or without PCV chemotherapy
 in patients with unfavorable low-grade glioma.

 OUTLINE: This is a randomized study. Patients are stratified according to tumor subtype
 (astrocytoma [mixed-astro dominant or equal astro/oligo mix] vs oligodendroglioma
 [mixed-oligo dominant]), age (younger than 40 vs at least 40), Karnofsky performance status
 (60-80% vs 90-100%), and contrast enhancement on preoperative scan (present vs absent).
 Patients with low-risk disease (younger than 40 years old whose tumors have been surgically
 removed) are assigned to arm I. Patients with high-risk disease (at least 40 years old or who
 have had incomplete tumor removal) are randomized to arm II or III.

 -  Arm I (low-risk patients): Patients are observed. Patients may receive treatment if
 tumor recurs.

 -  Arm II (high-risk patients): Patients receive daily external beam radiotherapy 5 days a
 week for 6 weeks.

 -  Arm III (high-risk patients): Patients receive radiotherapy as in arm II followed by
 chemotherapy 1 month later. Chemotherapy consists of oral lomustine on day 1,
 vincristine IV on days 8 and 29, and oral procarbazine on days 8-21. Each course of
 chemotherapy lasts 8 weeks. Patients may receive up to 6 courses of chemotherapy.

 Patients are followed every 4 months for 1 year, every 6 months for 2 years, and then
 annually thereafter.

 PROJECTED ACCRUAL: Approximately 252 patients will be accrued within 5.25 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed unifocal or multifocal supratentorial WHO grade II
 astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic), oligodendroglioma, or
 oligoastrocytoma

 -  Patients with neurofibromatosis are eligible

 -  No other low-grade histologies, including:

 -  Pilocytic astrocytoma

 -  Subependymal giant cell astrocytoma of tuberous sclerosis

 -  Subependymoma

 -  Pleomorphic xanthoastrocytoma

 -  Presence of a neuronal element such as ganglioglioma

 -  Dysneuroembryoplastic epithelial tumor

 -  No presence of any high-grade glioma, including:

 -  Anaplastic astrocytoma

 -  Glioblastoma multiforme

 -  Anaplastic oligodendroglioma

 -  Anaplastic oligoastrocytoma

 -  No tumors in nonsupratentorial or other locations including optic chiasm, optic
 nerve(s), pons, medulla, cerebellum, or spinal cord

 -  No evidence of spread to spinal meninges or noncontiguous cranial meninges (i.e.,
 leptomeningeal gliomatosis)

 -  No gliomatosis cerebri

 PATIENT CHARACTERISTICS:

 Age:

 -  18 and over

 Performance status:

 -  Karnofsky 60-100%

 Hematopoietic:

 -  For high-risk patients:

 -  Granulocyte count at least 1,500/mm^3

 -  Platelet count normal

 Hepatic:

 -  Bilirubin no greater than 2 times normal

 -  SGOT or SGPT no greater than 4 times normal

 -  Alkaline phosphatase no greater than 2 times normal

 Renal:

 -  Creatinine no greater than 2 times normal

 Pulmonary:

 -  No chronic lung disease (unless DLCO at least 60%)

 Neurological:

 -  Neurologic function score no greater than 3

 Other:

 -  Not pregnant or nursing

 -  Fertile patients must use effective contraception

 -  No other malignancy within the past 5 years except carcinoma in situ of the cervix or
 nonmelanoma skin cancer

 -  No active infection

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  Not specified

 Chemotherapy:

 -  No prior chemotherapy

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  No prior radiotherapy to the head or neck (unless brain is clearly excluded, such as
 radiotherapy for localized vocal cord cancer)

 Surgery:

 -  Not specified