Fluorouracil, Leucovorin, Gemcitabine, and Cisplatin in Treating Patients With Metastatic or Unresectable Adenocarcinoma of the Urothelium or Urachal Remnant

OBJECTIVES:

Primary

- Determine the response rate and overall survival of patients with metastatic or
unresectable adenocarcinoma of the urothelium or urachal remnant treated with
fluorouracil, leucovorin calcium, gemcitabine, and cisplatin.

Secondary

- Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to diagnosis (adenocarcinoma of the urothelium vs
adenocarcinoma of the urachal remnant).

Patients receive fluorouracil by vein (IV) continuously, leucovorin calcium IV once daily,
and cisplatin IV once daily on days 1-5 and gemcitabine IV on days 1 and 5. Courses repeat
every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 23-46 patients (7-18 with adenocarcinoma of the urachal remnant
and 16-28 with adenocarcinoma of the urothelium) will be accrued for this study.

Inclusion Criteria:

1. Histologic proof of cancer originating from the urinary tract with adenocarcinoma as
the predominant (>/= 50%) histology. Dr. Czerniak and/or Dr. Tamboli will be consulted
in equivocal cases of mixed histology. The Study Chairman is the final arbiter in
questions of mixed histology.

2. Bi-dimensionally measurable disease. All patients must have measurable or evaluable
disease. In general, liver and lung lesions should be at least 1 cm, and patients with
node-only disease should have lesions of >/= 1.5 cm in greatest dimension. Patients
with disease confined to bone may be eligible if a measurable lytic defect, or
soft-tissue component in present. Those without measurable disease may be eligible if
a serum marker is elevated (>/= 4 x ULN) (ie: CEA, CA-125, CA19-9, bhCG, etc).

3. (# 2 cont'd) The Study Chairman is the final arbiter in questions related to
measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on
bladder examination under anesthesia are considered to have measurable disease.

4. Patients are eligible if they have evidence of metastatic disease, or if their tumor
is surgically unresectable. In the absence of grossly metastatic disease, all patients
should be seen and evaluated by a member of the Urology staff to assess their
potential for resection.

5. Patients must have adequate physiologic reserves as evidenced by: • Life expectancy of
at least 9 months (based on co-morbidity) & at least 9 weeks based on the natural
history of their cancer. • Zubrod Performance Status (PS) of onset and due entirely to the cancer and not to comorbidity, and especially if the
compromised performance status is due to uncontrolled pain which is expected to be
rapidly reversible when therapy starts.

6. (#5 cont'd) • Adequate bone marrow function as defined by absolute neutrophil count
>/= 1,800 and platelet count >/= 150,000. Supranormal values judged to be of benign or
inconsequential etiology are acceptable. • Transaminase (either SGPT or SGOT) the upper limit of normal. • Conjugated bilirubin Creatinine clearance (either measured or estimated using the formula of Cockcroft and
Gault) of >/= 35 mL/min: CLcr = [(140-age) • wt(kg)]/[72 •Creat (mg/dL)] (For females,
x 0.85)

7. Patients must sign an informed consent indicating that they are aware of the
investigational nature of this study, in keeping with the policies of this hospital.

8. Patients must be at least 6 weeks out from pelvic irradiation, and must not have had
more than 10% of the bone marrow irradiated.

9. Patients with a history of cardiac disease, or evidence of ischemic heart disease on
EKG must have adequate cardiac function with an EF >/= 40% to participate.

10. Patient must be at least 18 years of age to participate in this study.

Exclusion Criteria:

1. Patients with metastases to the bladder from a primary adenocarcinoma arising outside
the urinary tract are ineligible.

2. Overt psychosis or mental disability or otherwise incompetent to give informed
consent.

3. A life threatening illness (unrelated to tumor) that would prevent completion of
protocol therapy.

4. Pregnant or nursing women, as the drug therapy regimen, and support medications pose
significant potential risks to the fetus and newborn.

5. Patients with second malignancies are eligible provided that the expected outcome from
the second cancer is such that this will not interfere in the delivery of this
therapy, or the assessment of response.

6. Patients with uncontrolled CNS metastases are not eligible.