Royal Marsden phase III trial of fluorouracil with or without interferon alfa-2b in advanced colorectal cancer.

Abstract

At the doses and schedules used in this study, IFN affords no benefit to 5-FU in terms of response and survival and significantly increases toxicity for patients with advanced colorectal cancer.

Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy

“…infusion, followed by a weekly 750 mg m-2 i.v. bolus with or without 9 million units of interferon-alpha2b s.c. three times per week was also used (Hill et al, 1995). The third study is a recent phase II investigation (Adenis et al, 1994) of the new TS inhibitor, Tomudex (ZD 1694) (Jackman et al, 1991(Jackman et al, , 1995b.…”

A phase II study of recombinant interferon-β (r-hIFN-β 1a) in combination with 5-fluorouracil (5-FU) in the treatment of patients with advanced colorectal carcinoma

“…Since the reported response rates of 5-FU in combination with interferons overlap those reported for 5-FU alone, results of randomized studies are required to substantiate the proposition that this combination demonstrates significant synergy in vivo. A recent study (Hill et al, 1995) failed to demonstrate a benefit of IFN-x in 106 patients randomized to receive the 5-FU regimen described in this study with or without IFN-ax. Toxicity was significantly greater in the IFN-ox-treated patients.…”

“…Several studies indicate that 5-FU and IFN-a act in synergy to inhibit the growth of tumour cell lines in vitro (Wadler and Schwartz, 1990), and in some clinical studies this combination results in response rates (35-62%) higher than that predicted for 5-FU alone (Pazdur et al, 1990;Wadler and Wiernick, 1990;Wadler et al, 1991). However, this activity has not been confirmed in other trials (Corfu-A Study Group, 1995;Hill et al, 1995) Although IFN-,B has only 30% homology with interferon-a (de Grado et al, 1982), it binds with greater affinity to certain subclasses of interferon receptors (Ruzicka et al, 1987). In laboratory studies, r-hIFN-P-la exhibits greater antiproliferative activity than IFN-a against some tumour cell lines (Borden et al, 1982) and, against colorectal carcinoma cell lines, it demonstrates both direct antiproliferative activity and synergy in combination with 5-FU (Wong et al, 1989;Kase et al, 1993).…”

Alpha-interferon does not increase the efficacy of 5-fluorouracil in advanced colorectal cancer

“…Patients Treatment arms 5FU vs. 5FU + α-IFN, with 5FU bolus RICRC 245 5FU 750 mg/m 2 /d continuous infusion d1 to d5, then weekly on bolus Greco et al, 1996 Same + α-IFN 9 MU three times a week Palermo 169 5FU 750 mg/m 2 /d bolus d1 to d5; then weekly Palmeri et al, 1998 Same + α-IFN 9 MU three times a week Ancona 141 5FU 500 mg/m 2 /d bolus d1 to d5; then weekly Piga et al, 1996 Same + α-IFN 3 MU/d RMH 106 5FU 750 mg/m 2 /d continuous infusion d1 to d5; then weekly on bolus Hill et al, 1995a Same + α-IFN 10 MU three times a week France 106 5FU 750 mg/m 2 /d continuous infusion d1 to d5; then weekly on bolus Dufour et al, 1996 Same + α-IFN 9 MU three times a week…”