We observed synergism between 5-fluorouracil(5-FU) and recombinant interferon-gamma (IFN-r) against 2 human colon cancer cell lines. Based on the in vitro study, we conducted a phase II trial of 5-FU and IFN-r in 45 patients with advanced
colorectal
cancer with measurable lesions between June 1990 and October 1991. 5-FU was administered as a loading schedule, 12mg/kg/day daily for 4 days by intravenous bolus followed by 4 half doses on alternate days. Ten days after completion of the loading
course
the weekly doses of 15mg/kg/day(not to exceed 1g) were given.
IFN-r, 2*10E6 IU/M*, was administered intramuscularly three times per week. Patients were categorized into 3 groups as previously untreated group, recurrent and refractory group. Recurrent group consisted of 6 patients who had relapsed after the
completion of adjuvant chemotherapy and refractory group consisted of 18 patients who had failed while receiving adjuvant or pallative chemotherapy. Among 41 evaluable patients the response rate were 35%, 50%, 6% for previously untreated,
recurrent
and
refractory group, respectively. (P<0.005) With a median follow-up of 30 weeks, median survivals of previously untreated group and refractory group were 42 weeks and 43 weeks. In recurrent group, median survival had not been reached, with a median
follow-up of 30 weeks. (P<0.005)
NK activity and immunophenotyping of peripheral blood lymphocytes following this combination therapy were not changed significantly. Clinical response was not correleated to changes in NK activity.
Common toxicities were flu-like symptoms(35%), leukopenia(28%), stomatitis(18%) and diarrhea(7%). But only 1% of patients developed grade 3 toxicity.
We conclude that the combination of 5-FU and IFN- r is an active and safe regimen against advanced colorectal cancer in previously untreated or relapsed patients.
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