Combination Chemotherapy for Patients With Brain Cancer
Combination Chemotherapy for Patients With Brain Cancer
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.

 PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy using
 paclitaxel and topotecan, plus G-CSF, in treating patients with glioblastoma multiforme or
 anaplastic astrocytoma that is refractory or recurrent.
OBJECTIVES: I. Determine the response rate in patients with refractory or recurrent
 glioblastoma multiforme or anaplastic astrocytoma treated with paclitaxel (TAX) and topotecan
 (TOPO) with granulocyte colony-stimulating factor (G-CSF) support. II. Determine survival in
 these patients. III. Describe the toxicity of TAX/TOPO/G-CSF. IV. Evaluate tumor p53
 expression in relation to response to TAX/TOPO/G-CSF.

 OUTLINE: All patients receive paclitaxel, topotecan, and G-CSF every 3 weeks for at least 2
 courses and until 2 courses beyond maximum response. Patients are followed every 3 months for
 2 years, then every 6 months for relapse and survival.

 PROJECTED ACCRUAL: A total of 35 patients will be entered if there are 1-3 responses in the
 first 20 patients.
DISEASE CHARACTERISTICS: Biopsy proven glioblastoma multiforme or anaplastic astrocytoma
 Central pathologic review at Dartmouth-Hitchcock Medical Center, including assay for tumor
 p53 expression No anaplastic oligodendroglioma No mixed oligodendroastrocytoma Recurrent or
 progressive disease following radiotherapy documented by CT or MRI within 2 weeks of entry

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60%-100%
 Hematopoietic: WBC at least 3,000 ANC at least 1,500 Platelets at least 100,000 Hepatic:
 Bilirubin no greater than 1.0 mg/dL AST/ALT no greater than 2.5 times normal Renal:
 Creatinine no greater than 1.5 mg/dL Other: No documented sensitivity to E. coli-derived
 products No major medical or psychiatric illness that would interfere with therapy or
 compliance with scheduled follow-up No pregnant or nursing women Adequate contraception
 required of fertile patients

 PRIOR CONCURRENT THERAPY: No prior taxanes or topoisomerase I inhibitors At least 4 weeks
 since chemotherapy (6 weeks since nitrosoureas) At least 4 weeks since radiotherapy