Wj. John et al., 5-FLUOROURACIL AND INTERFERON-ALPHA-2A IN ADVANCED COLORECTAL-CANCER - RESULTS OF 2 TREATMENT SCHEDULES, Cancer, 72(11), 1993, pp. 3191-3195
Background. Potential synergy between 5-fluorouracil (5-FU) and interf
eron alpha-2a (IFN-alpha-2a) has been demonstrated in the treatment of
colorectal carcinoma. Continuous low-dose infusion of 5-FU may have s
uperior response rates to bolus 5-FU in these malignancies. This repor
t presents results of two Phase II trials using these principles in co
lorectal cancer. Methods. Forty-eight patients were entered onto two p
rotocols; 18 were treated with 5-FU by a bolus infusion schedule with
concurrent IFN-alpha-2a (Group 1). Thirty patients were treated with c
ontinuous low-dose 5-FU and IFN-alpha-2a thrice weekly (Group 2). Resu
lts. The overall response rates were 33% (95% confidence interval [CI]
, 16-68%) and 33% (95% CI, 17-53%), respectively, for Groups 1 and 2.
In Group 2, in 16 previously untreated patients, there was a response
rate of 56% (95% CI, 30-80%). The median survival was 11 months and 6
months for Groups 1 and 2, respectively. Toxicity in Group 1 was as ex
pected, except the incidence of central nervous system toxicity was lo
w, with only one patient requiring dose reduction because of cerebella
r ataxia. The toxicity in Group 2 was substantial, with four patients
being removed from study because of toxicity and all patients treated
for more than 2 months requiring dose reductions. The most common (67%
) toxicity was mucositis, with 33% of those patients classified as Gra
de III or IV (Southwest Oncology Group criteria). Other major toxiciti
es were fatigue and hand/foot syndrome. Conclusions. The first trial c
onfirms previous response rate data for bolus injection 5-FU and IFN-a
lpha-2a. The second trial of low-dose continuous infusion 5-FU with IF
N-alpha-2a demonstrates similar efficacy with substantially greater to
xicity.