OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of sarcosinamide nitrosourea in patients with metastatic or unresectable solid tumors.
• Determine an appropriate oral dose of this drug for phase II study.
• Determine the oral bioavailability of this drug in these patients.
• Characterize the plasma pharmacokinetics of this drug in these patients.
• Evaluate response to treatment with this drug in patients with measurable or evaluable disease.
• Correlate, if possible, pharmacodynamics of this drug with toxicity and/or response in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral sarcosinamide nitrosourea (SarCNU) on days 1, 5, and 9. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SarCNU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4-5 weeks posttreatment.

PROJECTED ACCRUAL: A total of 21-46 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or unresectable solid tumors refractory to standard therapy or for which no curative or standard palliative therapy exists
• No leukemia or primary CNS malignancies

• CNS metastases allowed if:

  • No concurrent anticonvulsant therapy (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or felbamate)
  • Expected survival for at least 2 courses of therapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 2 months

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT or SGPT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min

Pulmonary:

• DLCO at least 80% of predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled serious medical or psychiatric illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy and recovered
• No prior nitrosourea or bleomycin

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since major surgery and recovered

Other:

• No concurrent enzyme-inducing anticonvulsants