Temozolomide in Treating Patients With Recurrent or Progressive Malignant Glioma

A Phase II Study of Temozolomide in the Treatment of Recurrent Malignant Gliomas

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of temozolomide in treating patients who have recurrent or progressive malignant glioma.

OBJECTIVES:

• Determine the progression-free survival and response rate of patients with recurrent or progressive malignant glioma treated with temozolomide.
• Determine whether certain categories of malignant gliomas, such as oligodendroglioma, are more sensitive to temozolomide.
• Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to histologic categories (recurrent glioblastoma multiforme [closed to accrual 11/30/01] vs recurrent anaplastic astrocytoma vs recurrent anaplastic oligodendroglioma).

Patients receive oral temozolomide twice daily for 5 consecutive days. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically proven recurrent or progressive malignant glioma of one of the following types:

  • Anaplastic oligodendroglioma or oligoastrocytoma
  • Anaplastic astrocytoma
  • Glioblastoma multiforme (stratum closed to accrual 11/30/01)

• Patients who have failed radiotherapy are eligible

• Measurable disease by CT scan or MRI

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic:

• SGOT or SGPT less than 3 times upper limit of normal (ULN)
• Alkaline phosphatase less than 2 times ULN (if greater than 2 times ULN then a gamma glutamyl transferase test must be performed)

Renal:

• BUN less than 1.5 times ULN
• Creatinine less than 1.5 times ULN

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No other serious concurrent infection or other medical illness that would preclude study entry
• No frequent vomiting or partial bowel obstruction
• HIV negative
• No AIDS-related illness
• No other concurrent malignancy except carcinoma in situ of the cervix or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent epoetin alfa

Chemotherapy:

• At least 6 weeks since other prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 3 months since prior radiotherapy (exceptions allowed for recurrent/progressive disease at discretion of primary investigator)

Surgery:

• Recovered from prior surgery

Other:

• No other concurrent investigational agents
• Concurrent anticonvulsant therapy allowed