Treatment of active Crohn's disease with onercept (recombinant human soluble p55 tumour necrosis factor receptor): results of a randomized, open-label, pilot study.

BACKGROUND: Monoclonal antibodies to the pro-inflammatory cytokine tumour necrosis factor-alpha have shown efficacy in treating Crohn's disease, but can be immunogenic. Soluble tumour necrosis factor-binding proteins are being studied as potential alternative anti-tumour necrosis factor agents in Crohn's disease. AIM: To investigate the safety and efficacy of onercept, a recombinant form of the natural human soluble p55 tumour necrosis factor receptor, in the treatment of patients with active Crohn's disease. METHODS: In a pilot study, 12 patients with active Crohn's disease were randomized to receive onercept at either 11.7 or 50 mg three times weekly for 2 weeks. Patients were followed up for 6 months after the end of treatment. RESULTS: The Crohn's disease activity index decreased rapidly during treatment in both groups. Seven responses (Crohn's disease activity index decrease of 100 points) were observed over the first 6 weeks of the study, including five remissions (Crohn's disease activity index decrease of 150 points). Improvement was sustained for 2-4 months after stopping treatment. Treatment was well tolerated. No patients developed antibodies to onercept. CONCLUSIONS: Neutralizing the activity of tumour necrosis factor-alpha with its soluble p55 receptor may be valuable in the treatment of patients with Crohn's disease. Larger placebo-controlled trials are indicated.

A randomized phase II trial of 5-fluorouracil, with or without human interferon-beta, for advanced colorectal cancer.

This study compared the efficacy and safety of 5-fluorouracil (5-FU) monotherapy to that of 5-FU combined with natural human interferon-beta (IFN-beta) in patients with unresectable, advanced colorectal carcinoma. Forty-nine chemotherapy-naive patients were randomized to 5-FU alone or to the combination. All patients received 750 mg m(-2) day(-1) 5-FU for 5 days by continuous intravenous (i.v.) infusion, followed after day 15 by a weekly i.v. bolus of 750 mg m(-2). IFN-beta was injected intramuscularly three times weekly at 9 M IU. Treatment continued for 52 weeks, or until disease progression or intolerable toxicity. Clinical endpoints were tumor response, time to progression, survival and toxicity. The addition of IFN-3 to 5-FU significantly improved response rate (33.3% vs 4.5% for evaluable patients; P = 0.021), time to progression (median 7.2 vs 4.2 months; P = 0.0435), and survival time (median 15.9 vs 7.2 months; P = 0.038) without significantly increasing toxicity compared to 5-FU alone. Cumulative 5-FU dose was higher with combined therapy (P < 0.001): more patients receiving monotherapy discontinued treatment because of disease progression. Fever was more frequent with combined therapy (P = 0.008); there were no other differences in toxicity. The only grade IV toxicity observed was neutropenia (two patients per group). A randomized phase III trial has been initiated to confirm the synergy between 5-FU and IFN-beta.

The effect of postoperative normovolaemic anaemia and autotransfusion on blood saving after internal mammary artery bypass surgery.

The efficacy of two blood conservation techniques in decreasing and in preventing the use of homologous blood products was retrospectively studied in 150 patients undergoing internal mammary artery bypass surgery. Patients were matched according to prebypass blood haemoglobin (Hb) content and body surface area and were allocated to one of three groups: in the patients of group 1 (n = 50), normovolaemic anaemia (NA) was accepted postoperatively (haematocrit [Hct] was accepted to a minimum level of 25%); the patients of group 2 (n = 50) were treated with postoperative autotransfusion (AT) of mediastinal shed blood and acceptance of NA. Group 3 (n = 50) contained control patients, not treated with NA or with AT (Hct was accepted to a minimum level of 30%). Patients of group 1 required 3.0 +/- 0.3 units of homologous blood products, but the patients of groups 2 and 3 received significantly more (p less than 0.01) units: 3.9 +/- 0.2 and 4.5 +/- 0.3 units. No donor blood products were needed in 36%, 9% and 5% of the patients in groups 1, 2 and 3 respectively. The net postoperative blood loss was similar in the groups: 1229 +/- 92 ml in group 1, 1098 +/- 74 ml in group 2 and 1243 +/- 72 ml in group 3. However, total blood loss (1982 +/- 135 ml), including the retransfused part (954 +/- 89 ml), was significantly larger (p less than 0.01) in group 2, than in groups 1 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)