Trial Information

A Phase II Study of 5-Fluorouracil Administered as a One Hour Infusion in Combination With Calcium Leucovorin and Interferon Alpha-2A in Advanced Colorectal Cancer

This protocol will evaluate the activity of 5-Fluorouracil (FUra) given as a 1 hour infusion
in combination with leucovorin (LV) and interferon IFN alpha-2a in patients with advanced,
measurable colorectal cancer. IFN alpha-2a will be given at 5 million U/m(2) SC days 1-6;
LV, 200 mg/m(2), will be given as a short infusion over 30 minutes days 2-6, followed
immediately by a 1 hour IV infusion of FUra days 2-6. The starting dose of FUra will be 425
mg/m(2)/d(1). Cycles will be repeated at three week intervals provided that the granulocyte
count and platelet count have recovered to >e; 1200/microL and >e; 80,000/microL,
respectively, and all non-hematologic toxicity has resolved. The dose of FUra will be
adjusted according to individual tolerance. Preliminary experience with FUra given as a 1
hour infusion suggests that it is less toxic. The primary goal of this study is to
determine if this less toxic regimen retains clinical antitumor activity. FUra plasma
samples will be obtained the initial cycle at 50 and 55 minutes during the first 1 hour
infusion of FUra to permit documentation of achieved plasma levels and to permit correlation
between FUra pharmacokinetics and clinical toxicity and/or response. Pharmacokinetic
sampling will be repeated if the dose of FUra is increased or decreased in subsequent
cycles.

Patients will be stratified according to whether or not they have received prior adjuvant
chemotherapy. A two-stage design will be employed for patients with no prior chemotherapy:
If less than or equal to 4 responses are seen among the initial 20 previously untreated
patients, accrual will cease. If greater than or equal to 5 responses are seen in the
initial 20 patients, however, accrual will be expanded to 40 patients.

Fourteen patients who have received prior adjuvant chemotherapy (completing it at least 6
months prior to study entry) or have received prior FUra only as a radiation sensitizer will
be entered. If no responses are seen, accrual to this cohort will cease. If greater than
or equal to 1 response is seen, accrual may be expanded to 24 patients.