Procarbazine in Treating Patients With Recurrent Brain Tumor

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

PURPOSE: Phase I/II trial to study the effectiveness of procarbazine in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme following treatment with radiation therapy.

OBJECTIVES:

* Determine the maximum tolerated dose of oral procarbazine when administered to patients with recurrent glioma receiving or not receiving anticonvulsants metabolized by the P450 hepatic enzyme complex.
* Determine the pharmacokinetics of oral procarbazine, including any effects of hepatic enzyme inducing drugs, in these patients.
* Assess the response rate to procarbazine in these patients.
* Evaluate this regimen in terms of overall survival and duration of disease free survival in these patients.
* Evaluate the toxicity of this regimen in these patients.

OUTLINE: Phase I of this study is a dose escalation study. Patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs no drugs or modest-induction drugs).

* Phase I: Patients receive oral procarbazine once daily for 5 days. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of oral procarbazine until the maximum tolerated dose (MTD) is determined.

* Phase II: Once the MTD is determined, patients receive procarbazine as in Phase I.

Patients are followed every 2 months until death.

PROJECTED ACCRUAL: A total of 24-35 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically proven malignant glioma of one of the following types:

  * Anaplastic astrocytoma
  * Anaplastic oligodendroglioma
  * Glioblastoma multiforme
* Progressive or recurrent disease after radiotherapy with or without chemotherapy
* Measurable disease by serial MR or CT

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Greater than 2 months

Hematopoietic:

* Absolute neutrophil count at least 1500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* SGPT/SGOT no greater than 4 times upper limit of normal

Renal:

* Creatinine no greater than 1.7 mg/dL

Other:

* No serious concurrent infection
* No other illness that would preclude study
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent filgrastim (G-CSF) during the first course

Chemotherapy:

* See Disease Characteristics
* No more than 1 prior chemotherapy regimen
* At least 3 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas)
* No more than 2 prior courses of carmustine or lomustine and no greater than 460 mg/m2 or 220 mg/m2, respectively
* No prior procarbazine

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics
* At least 3 months since prior radiotherapy

Surgery:

* Prior surgery allowed

Other:

* Recovered from toxicity of prior therapy
* At least 10 days since prior anticonvulsants for patients in Arm II
* No concurrent investigational agents
* No concurrent ethanol, ephedrine, isoproterenol, epinephrine, tricyclic antidepressants, paragyliline, narcotic analgesics, antihistamines, phenothiazines, hypotensives, or barbiturates
* At least 14 days since prior antidepressants (e.g., SSRI and/or MAO inhibitor)
* Must avoid foods high in tyramine (i.e., dark beer, wine, yogurt, cheese, bananas)