Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced colorectal carcinoma

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