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.

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)