Combination Chemotherapy and Bone Marrow Transplantation or Peripheral Stem Cell Transplantation in Treating Patients With Oligodendroglioma

OBJECTIVES:

• Determine the duration of response in patients with newly diagnosed pure and mixed anaplastic oligodendrogliomas treated with intensive chemotherapy supported by autologous transplantation.
• Determine the neurological and systemic toxic effects of this regimen in these patients.
• Determine the relationship of 1p loss of heterozygosity on radiographic response, progression-free survival, and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Mobilization and stem cell harvest: Patients receive filgrastim (G-CSF) subcutaneously daily for up to 7 days followed by peripheral blood stem cell (PBSC) or bone marrow (BM) harvest.
• Induction therapy: All patients then receive induction therapy (PCV) comprising of oral lomustine on day 1, vincristine IV on days 8 and 29, and oral procarbazine on days 8-21. Treatment repeats every 42 days in the absence of progressive disease or unacceptable toxicity. Patients with prior complete resections receive 3 courses of PCV then proceed to high-dose chemotherapy and transplantation as described below, provided tumor has not recurred. Patients with prior partial resections or biopsies receive 2 courses of PCV and are assessed for response; those who achieve complete response (CR) or major partial response (PR) receive 1 more course of PCV. Patients who achieve partial response or have stable disease receive 2 more courses of PCV and are reassessed.
• High-dose chemotherapy and transplantation: Patients who achieve CR or PR receive thiotepa IV on days -8 to -6 and busulfan IV over 2 hours on day -5 to -3. Patients undergo autologous BM or PBSC transplantation on day 0.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 3-5 years.

DISEASE CHARACTERISTICS:

• Histologically proven anaplastic oligodendroglioma OR
• Histologically proven anaplastic mixed glioma (oligoastrocytoma) provided there is an unequivocal and substantial (at least 25%) oligodendroglial element
• No systemic or leptomeningeal metastases (excluding contiguous leptomeninges)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) OR
• SGOT no greater than 2 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• LVEF at least 50%

Pulmonary

• DLCO at least 50% of predicted

Other

• No other serious illness that would preclude study therapy
• No other concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior cranial radiotherapy

Surgery

• Prior complete or partial resection, open biopsy, or stereotactic biopsy allowed