Procarbazine and Isotretinoin in Treating Patients With Recurrent Primary Malignant Gliomas
Procarbazine and Isotretinoin in Treating Patients With Recurrent Primary Malignant Gliomas
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Combining more than one drug may kill more tumor cells. It is not
 yet known whether giving procarbazine alone or with isotretinoin is more effective for
 recurrent primary malignant glioma.

 PURPOSE: Randomized phase III trial to compare the effectiveness of procarbazine alone or
 with isotretinoin in treating patients with recurrent primary malignant gliomas.
OBJECTIVES: I. Determine whether the combination of isotretinoin and procarbazine can improve
 time to progression and survival compared to procarbazine alone in patients with recurrent
 malignant gliomas. II. Document the toxicity of these two regimens in these patients.

 OUTLINE: This is a randomized, multicenter study. Patients are randomized to receive
 procarbazine alone or in combination with isotretinoin. Arm I: Patients receive oral
 procarbazine once daily on days 1-14 every 28 days. Oral isotretinoin is administered every
 12 hours on days 15-28 every 28 days. Patient receive 6 courses of combined therapy, then
 continue with oral isotretinoin alone on days 15-28 of each 28 day course, until disease
 progression or unacceptable toxicity. Arm II: Patients receive procarbazine by mouth once
 daily on days 1-14 followed by 2 weeks of rest. Patients receive a total of 6 courses of
 treatment in the absence of disease progression and unacceptable toxicity. Patients are
 followed until death.

 PROJECTED ACCRUAL: This study will accrue a total of 194 patients (97 per treatment group).
DISEASE CHARACTERISTICS: Histologically proven primary malignant gliomas including the
 following: Glioblastoma multiforme Gliosarcoma Anaplastic astrocytoma Anaplastic
 oligodendroglioma Anaplastic infiltrating glioma Mixed malignant gliomas Must show evidence
 of tumor recurrence or progression on at least 2 serial enhanced MRI scans Must have
 measurably enhancing residual disease on MRI or CT scan of brain

 PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Karnofsky 60-100% Life
 expectancy: Greater than 8 weeks Hematopoietic: Absolute granulocyte count at least
 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGPT less than 2 times institutional
 normal Alkaline phosphatase less than 2 times institutional normal Bilirubin less than 1.5
 mg/dL Renal: BUN less than 1.5 times institutional normal OR Creatinine less than 1.5 times
 institutional normal Other: No active infection Not pregnant or nursing Fertile patients
 must use effective contraception 1 month before, during, and 1 month after study No other
 disease that will obscure toxicity or alter drug metabolism No other concurrent medical
 illness

 PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
 procarbazine No prior isotretinoin At least 4 weeks since prior chemotherapy (6 weeks for
 nitrosoureas) and recovered Endocrine therapy: Not specified Radiotherapy: Prior
 radiotherapy allowed Surgery: Not specified Other: No concurrent tetracyclines