OBJECTIVES:

• Classify patients with solid tumors or lymphoma according to UGT1A1 promoter (TATA box) and coding region (Gly71Arg) mutation, and CYP3A4 promoter (G to A) polymorphisms.
• Identify UGT1A1 enzyme glucuronidator and irinotecan oxidizer phenotypes in these patients and determine the correlation between the two metabolic reactions in vivo.
• Determine the relationship between UGT1A1 genotype (promoter and/or coding region mutation) and CYP3A4 promoter genotype vs gastrointestinal or bone marrow toxicity, and pharmacokinetics of irinotecan in these patients.
• Determine the pharmacokinetics of irinotecan in these patients.

OUTLINE: Patients are genotyped for UGT1A1 enzyme and classified as "Gilbert's" (7/7), "heterozygotes" (6/7), and "homozygotes for allele 6" (6/6). The DNA is analyzed for the UGT1A1 coding region mutation (Gly71Arg) and CYP3A4 promoter polymorphism. Patients are also examined for glucuronidator ratio of SN-38, the active metabolite of irinotecan, and classified as "low/slow" (very low or zero SN-38G/SN-38 ratio), "intermediate" (less than 50% normal ratio), or "normal".

Patients receive irinotecan IV over 90 minutes once every 3 weeks. Treatment continues for at least 2 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 20 months.

DISEASE CHARACTERISTICS:

• Histologically proven solid tumor or lymphoma

  • Responded to irinotecan OR no existing curative therapy
• No leukemia
• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3500/mm^3
• Absolute neutrophil count at least 1500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• SGOT/SGPT less than 5 times upper limit of normal (unless due to disease)

Renal:

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

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No inflammatory bowel disease requiring therapy
• No chronic diarrhea syndrome or paralytic ileus

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 2 weeks since prior colony stimulating factor
• At least 4 weeks since prior biologic therapy
• No concurrent biologic therapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy to greater than 25% of bone marrow
• No concurrent palliative radiotherapy

Surgery:

• No prior transplant

Other:

• No concurrent substrates of UGT1A1 enzyme
• No concurrent inducers or inhibitors of UGT1A1 enzyme activity