RATIONALE: Chemotherapy drugs, such as fenretinide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether neoadjuvant and adjuvant fenretinide is more effective than adjuvant fenretinide alone.

PURPOSE: This randomized phase II trial is studying how well neoadjuvant and adjuvant fenretinide works compared to adjuvant fenretinide alone in treating patients who are undergoing surgical resection for recurrent glioblastoma multiforme.

OBJECTIVES:

• Compare the efficacy of neoadjuvant and adjuvant fenretinide vs adjuvant fenretinide alone, in terms of 6-month progression-free survival, in patients with recurrent glioblastoma multiforme undergoing surgical resection.
• Correlate the serum and glioma tissue pharmacology of this drug with clinical response in patients treated with these regimens.
• Determine whether this drug induces apoptosis in glioma tissue in patients treated with these regimens.
• Correlate the apoptotic index with tissue and serum concentration and clinical response in patients treated with these regimens.
• Compare radiological response, overall survival, and unexpected toxicity in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive neoadjuvant oral fenretinide twice daily for 1 week and then undergo surgical resection.
• Arm II: Patients undergo surgical resection. Beginning two weeks after surgery, all patients receive adjuvant oral fenretinide twice daily on weeks 1 and 4. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 21-46 patients (10-23 per treatment arm) will be accrued for this study within 7-46 months.

• Drug: fenretinide
• Procedure: adjuvant therapy
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme after initial tumor resection

• Radiologically evident recurrent tumor after prior radiotherapy OR after treatment for no more than 2 prior relapses

  • Enhancing or nonenhancing recurrent disease by MRI
• No progressive symptoms requiring urgent surgery

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• PT/PTT no greater than upper limit of normal
• SGPT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal
• Bilirubin less than 1.5 mg/dL

Renal

• BUN no greater than 1.5 times normal OR
• Creatinine no greater than 1.5 times normal

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 2 months after study participation
• Amylase and lipase normal
• No active infection
• No other disease that would obscure toxicity or dangerously alter drug metabolism
• No other concurrent serious medical illness
• Not at risk from any study treatment delays
• Able to swallow fenretinide capsules

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Recovered from all prior chemotherapy
• Approximately 2 weeks since prior vincristine
• Approximately 6 weeks since prior nitrosoureas
• Approximately 3 weeks since prior procarbazine

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 1 week since prior vitamin A
• At least 1 week since prior isotretinoin (Accutane®)
• No concurrent vitamin A during and for 2 weeks after study participation
• No concurrent antioxidants (e.g., ascorbic acid or vitamin E)