PHASE-I TRIAL OF RECOMBINANT PLATELET FACTOR-4 (RPF4) IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA

Background: Recombinant platelet factor 4 (rPF4) is a naturally occurr ing protein found in platelet alpha granules that can inhibit angiogen esis. Methods: In this Phase I trial, 9 patients with metastatic color ectal cancer who had failed 5-FU treatment received rPF4 at doses rang ing from 0.3 to 3.0 mg/kg via 30-minute infusion. Three additional pat ients were treated with the 3 mg/kg dose over a B-hour period of infus ion. Results: The only toxicity encountered was mild leg twitching in 2/3 patients treated with the 6-hour infusion. One patient with a hist ory of phlebitis developed a lower extremity deep venous thrombosis af ter the first dose of rPF4. A mild rise in fibrinogen level was noted in several patients. Of the 11 evaluable patients, there were no clini cal responses to treatment. Conclusions: rPF4 is well tolerated at the doses and schedules tested. No clinical responses were observed. Prol onged infusion schedules should be investigated.