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.
- 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.
- Histologically or cytologically confirmed malignancy refractory to existing
chemotherapy or for which no standard therapy exists
- Evaluable disease
- 18 and over
- SWOG 0-2
- Greater than 3 months
- Absolute neutrophil count greater than 1,500/mm3
- Platelet count greater than 100,000/mm3
- Hemoglobin greater than 8.0 mg/dL
- Bilirubin less than 2.0 mg/dL
- AST less than 3.0 times upper limit of normal
- Creatinine no greater than 2.0 mg/dL
- No active infection requiring antibiotics
- Not pregnant or nursing
- Fertile patients must use effective barrier contraception
PRIOR CONCURRENT THERAPY:
- Not specified
- At least 3 weeks since prior systemic cytotoxic chemotherapy (including fluorouracil)
- No prior gemcitabine
- Prior hormonal therapy allowed
- No concurrent hormonal contraception
- At least 3 weeks since prior radiotherapy to large areas of active bone marrow and
- Prior major surgery allowed and recovered
- No prior or concurrent antiviral nucleosides
Philip A. Philip, MD, PhD, FRCP
Barbara Ann Karmanos Cancer Institute