I. Brunetti et al., DOUBLE 5-FLUOROURACIL MODULATION WITH FOLINIC ACID AND RECOMBINANT INTERFERON-ALPHA-2B - A PHASE-I-II STUDY IN METASTATIC COLORECTAL-CANCERPATIENTS, American journal of clinical oncology, 17(3), 1994, pp. 210-214
Twenty-two patients with metastatic colorectal cancer entered a Phase
I-II trial to assess the maximum tolerable dose of alpha-2B-interferon
administered intramuscularly three times per week in combination with
fixed doses of 5-fluorouracil (450 mg/m2 IV for 5 days, and, from day
28, weekly) and folinic acid (200 mg/m2 IV before 5-fluorouracil) and
the efficacy of this combination. Diarrhea and mucositis were the mos
t frequent 5-fluorouracil-related toxicities and were greater-than-or-
equal-to ECOG grade 3 in 23% and 18% of patients, respectively. Of 15
patients receiving interferon greater-than-or-equal-to 9 X 10(6) IU, 1
0 required interferon dose reduction mostly because of severe fatigue,
anorexia, and declining performance status. Among 19 patients evaluab
le for response, 3 achieved a partial response and 1 a complete respon
se for an overall response rate of 21% (95% confidence interval, 6-46%
). In conclusion, our study demonstrates that IFN-alpha2B at doses hig
her than 6 X 10(6) IU intramuscularly three times per week in the comb
ination with 5-fluorouracil and folinic acid we used is too toxic for
the majority of patients; this combination has moderate activity in me
tastatic colorectal cancer, although similar response rates have been
reported, with less toxicity, with 5-fluorouracil plus folinic acid wi
thout IFN-alpha. A larger Phase III study would be required to determi
ne the value of IFN-alpha in this combination.