Combination Chemotherapy In Treating Patients With Advanced Cancer

Phase I Study of Gemcitabine (Gemzar) and UFT/Leucovorin

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining gemcitabine, fluorouracil-uracil and leucovorin in treating patients who have advanced cancer that has not responded to previous therapy.

OBJECTIVES:

• Determine the maximum tolerated doses of gemcitabine, fluorouracil-uracil (UFT), and leucovorin calcium in patients with advanced refractory cancer.
• Assess the toxicity of this combination regimen in this patient population.
• Evaluate this regimen in terms of response rate, response duration, and overall survival in these patients.

OUTLINE: This is a dose escalation study of gemcitabine and fluorouracil-uracil.

Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Patients receive oral leucovorin calcium immediately followed by oral fluorouracil-uracil (UFT) three times a day on days 1-21. Courses are repeated every 28 days. Treatment continues in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignancy refractory to existing chemotherapy or for which no standard therapy exists
• Evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• SWOG 0-2

Life expectancy:

• Greater than 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3
• Hemoglobin greater than 8.0 mg/dL

Hepatic:

• Bilirubin less than 2.0 mg/dL
• AST less than 3.0 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• No active infection requiring antibiotics
• Not pregnant or nursing
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior systemic cytotoxic chemotherapy (including fluorouracil) and recovered
• No prior gemcitabine

Endocrine therapy:

• Prior hormonal therapy allowed
• No concurrent hormonal contraception

Radiotherapy:

• At least 3 weeks since prior radiotherapy to large areas of active bone marrow and recovered

Surgery:

• Prior major surgery allowed and recovered

Other:

• No prior or concurrent antiviral nucleosides