A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas

Inclusion 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)