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,
and leucovorin in treating patients with recurrent, refractory, or metastatic solid tumors
- Determine the clinical toxic effects associated with administering sequential
gemcitabine followed by fluorouracil with leucovorin calcium in patients with
refractory or recurrent or metastatic solid tumors or lymphomas.
- Determine achieved steady-state plasma levels of gemcitabine and fluorouracil in these
- Determine any antitumor activity of this regimen in these patients.
- Determine the pharmacodynamics of gemcitabine and fluorouracil in these patients.
OUTLINE: This is a dose-escalation study of fluorouracil and gemcitabine.
During the first course, patients receive gemcitabine IV over 30 minutes once weekly for 2
weeks followed by one week of rest. During subsequent courses, patients receive gemcitabine
as above followed immediately by fluorouracil IV over 24 hours once weekly for 2 weeks.
Patients also receive leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Sequential dose escalation of fluorouracil is followed by sequential dose escalation of
gemcitabine. Cohorts of 3-6 patients receive escalating doses of fluorouracil and then
gemcitabine until the maximum tolerated dose (MTD) of the combination is determined. The MTD
is defined as the dose preceding that at which 2 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A maximum of 108 patients will be accrued for this study.
- Diagnosis of cancer that has failed standard therapy or for which no such therapy
exists, including, but not limited to:
- Unresectable primary or recurrent solid tumors (e.g., colon, pancreatic, lung,
esophageal, or cholangiocarcinoma)
- Metastatic disease
- Lymphoma with no prior high-dose chemotherapy requiring autologous or allogeneic
stem cell rescue
- No leukemias
- No CNS metastases or primary CNS malignancies
- No failure on prior gemcitabine therapy
- 18 and over
- ECOG 0-2
- Not specified
- Absolute granulocyte count at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 2.0 mg/dL
- Transaminases less than 6 times upper limit of normal
- Creatinine no greater than 2.0 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other serious concurrent medical illness that would preclude study
- No active infections requiring IV antibiotics
- HIV negative
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- More than 4 weeks since prior immunotherapy and recovered
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy (at least 6 weeks for mitomycin or
nitrosoureas) and recovered
- At least 3 months since prior suramin
- At least 5 weeks since prior eniluracil (8 weeks prior to start of fluorouracil) and
- No steroid therapy if utilized for chronic lymphoma therapy
- At least 4 weeks since prior steroidal therapy as disease treatment
- At least 2 weeks since prior radiotherapy to no more than 20% of bone marrow
- At least 4 weeks since prior radiotherapy to 21% or more of bone marrow
- Recovered from prior radiotherapy
- Recovered from prior surgery
- No concurrent cimetidine