RATIONALE: Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining ifosfamide with O(6)-benzylguanine may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
• Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.
• Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.
• Determine the safety and toxicity of this regimen in these patients.

Secondary

• Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.
• Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.

OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.

• Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.

• Course 2: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive high-dose ifosfamide as in course 1.
  • Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.

Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.

• Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II.

In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover.

In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A minimum of 32 patients (at least 2 in arm I and at least 24 in arm II) will be accrued for this study within 12-15 months.

• Biological: filgrastim
• Drug: O6-benzylguanine
• Drug: ifosfamide

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

  • Unresectable, metastatic disease
  • No primary tumors
• Eligible for high-dose ifosfamide-based therapy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Karnofsky 70-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
• No prior hematopoietic stem cell transplantation
• No concurrent pegfilgrastim
• No concurrent immunotherapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent therapeutic radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior anticancer therapy
• No more than 2 prior cytotoxic regimens
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies
• No other concurrent investigational agents