RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining chemotherapy with peripheral stem cell
transplantation may allow the doctor to give higher doses of drugs and kill more tumor
PURPOSE: Phase I trial to study the effectiveness of high-dose topotecan and peripheral stem
cell transplantation in treating patients with refractory cancer.
- Determine the maximum tolerated dose, toxicities, and preliminary antitumor activity of
escalating doses of topotecan, with filgrastim (G-CSF) and peripheral blood stem cell
support, when administered to patients with refractory malignancies for which no
effective therapy exists.
OUTLINE: This is a dose-escalation study.
Prior to stem cell harvesting, patients receive 1-2 courses of mobilizing salvage
After stem cell harvest, high-dose topotecan is administered according to an escalating
dosage scale. Topotecan is given over 30 minutes daily for three days. A minimum of 3
patients are entered at each dose level. The MTD is defined as the dose immediately below
that at which 2 patients experience dose limiting toxicity.
Peripheral blood stem cells (PBSC) are infused at least 24 hours after treatment with
topotecan is complete. Filgrastim (G-CSF) is administered subcutaneously beginning on the
day PBSC are infused and continuing until blood counts recover.
Patients are followed every 3 months for 1 year and then every 6 months thereafter.
PROJECTED ACCRUAL: Not specified
- Histologically confirmed refractory malignancies for which no effective therapy is
- Over 18
- ECOG 0-2
- At least 3 months
- Platelet count at least 100,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Total bilirubin no greater than 2.0 mg/dL
- No chronic active hepatitis
- Creatinine clearance at least 60 mL/min
- Left ventricular ejection fraction greater than 45%
- DLCO greater than 60% of predicted
- HIV negative
- No active infection
- No concurrent medical condition that would preclude therapy
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- Not specified
- At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas or
- Not specified
- No radiotherapy to greater than 30% of bone marrow
- No wide field radiotherapy
- Recovered from any prior surgery