Observation or 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