OBJECTIVES: I. Determine the maximum tolerated doses and sequence of topotecan and ifosfamide that can be administered daily for 3 days on an every 4 week schedule in patients with refractory solid tumors. II. Evaluate toxicity of topotecan and ifosfamide when administered on this schedule in this patient population. III. Evaluate the pharmacokinetics related to sequencing of topotecan and ifosfamide and the more efficacious, less toxic schedule of treatment. IV. Assess the evidence of antineoplastic activity for this combination of agents.

OUTLINE: This is an open label, dose escalation study. Cohorts of 3-6 patients receive ifosfamide at an initial fixed dose plus escalating doses of topotecan by 30 minute infusion daily for 3 successive days. Cycle repeats every 28 days. After topotecan dosage is escalated for a total of 3 dose levels, then ifosfamide dose is escalated by one dose level. The first patient enrolled is treated with ifosfamide followed by topotecan for cycle 1, and for cycle 2 the order of drugs is reversed. The second patient is treated with the same drugs but with topotecan administered before ifosfamide in the first cycle and then reversed in the second cycle. From the third cycle onward, ifosfamide is followed by topotecan, but the first two cycles continue to alternate with each subsequent patient entered. Filgrastim (granulocyte colony-stimulating factor; G-CSF) is given for all cycles on days 5-12 or until the absolute granulocyte count has reached its nadir and recovered. If there is no dose limiting toxicity (DLT) in a cohort, new patients are entered at the next highest dose level. If 1 of 3 patients at any level experiences DLT, an additional 3 patients are treated at that level before proceeding to a higher level. If 2 or more patients experience DLT at any dose level, the level immediately preceding that level is defined as the maximum tolerated dose (MTD). Three more patients are treated at the MTD to ensure that no DLT is experienced at that level. After MTD is identified, 10 additional patients are accrued at that level. Patients with minor response, stable disease, or symptomatic or marker improvement may continue on treatment for up to 6 cycles. After 6 cycles, continuation on treatment is at the investigator's discretion.

PROJECTED ACCRUAL: There will be a maximum of 24 patients accrued into this study over 8 months.