Radiation Therapy or Temozolomide in Treating Patients With Gliomas

OBJECTIVES:

Primary

• Compare the progression-free survival of patients with low-grade gliomas treated with radiotherapy vs temozolomide.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Determine whether the incidence of late toxicity can be decreased in patients who are randomized to receive temozolomide.
• Compare the toxic effects of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, chromosome 1p status (deleted vs normal vs undeterminable), contrast enhancement on MRI (yes vs no), age (< 40 years vs ≥ 40 years), and WHO performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily, 5 days a week, for a total of 28 fractions (i.e., 5½ weeks).
• Arm II: Patients receive oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months until disease progression.

After completion of study treatment, patients are followed every 6 months for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A minimum of 699 patients (a total of 466 randomized [233 per treatment arm]) will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed low-grade glioma, including any of the following types:

• Astrocytoma (gemistocytic, fibrillary, or protoplasmatic)
• Oligoastrocytoma
• Oligodendroglioma
• WHO grade II disease
• Supratentorial tumor location only
• RTOG neurological function 0-3
• Not a candidate for surgical treatment alone
• Requires treatment, as determined by ≥ 1 of the following criteria:

• Age ≥ 40 years
• Radiologically-proven progressive lesion
• New or worsening neurological symptoms other than seizures only (e.g., focal deficits, signs of increased intracranial pressure, or mental deficits)
• Intractable seizures, defined by both of the following criteria:

• Experiences persistent seizures that interfere with everyday life activities except driving a car
• Failed 3 anti-epileptic drug regimens, including ≥ 1 combination regimen
• Tumor material (paraffin-embedded) or histopathologic slides available

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• No chronic hepatitis B or C infection
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No known HIV positivity
• No other serious medical condition
• No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer
• No psychological, familial, sociological, or geographical condition that would preclude study participation
• No medical condition that would preclude receiving oral medication (e.g., frequent vomiting or partial bowel obstruction)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors for elevating absolute neutrophil counts for the purpose of temozolomide administration
• No concurrent epoetin alfa
• No concurrent immunotherapy or biologic therapy

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the brain
• No concurrent integrated boost with intensity-modulated radiotherapy

Surgery

• Recovered from prior surgery
• No concurrent surgical tumor debulking

Other

• No prior randomization to this study
• No other concurrent investigational drugs
• No concurrent regular use of agents known to be radiosensitizers or radioprotectors (e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study radiotherapy

• Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed