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Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced colorectal carcinoma
N Belman1, E M Bonnem, H A Harvey
1Department of Medicine, M.S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA.
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.
Insights
Recombinant platelet factor 4 (rPF4) showed good tolerability in metastatic colorectal cancer patients. However, this anti-angiogenic agent did not demonstrate clinical responses in the trial.
Area of Science:
- Oncology
- Pharmacology
Background:
- Recombinant platelet factor 4 (rPF4) is an endogenous protein with demonstrated anti-angiogenic properties.
- Platelet alpha granules are the natural source of rPF4 within the body.
Purpose of the Study:
- To evaluate the safety and tolerability of rPF4 in patients with metastatic colorectal cancer.
- To assess the preliminary efficacy of rPF4 in this patient population.
Main Methods:
- A Phase I clinical trial was conducted involving 12 patients with metastatic colorectal cancer.
- Patients received varying doses of rPF4 (0.3 to 3.0 mg/kg) administered via 30-minute or 6-hour infusions.
- Treatment was administered to patients who had previously failed 5-fluorouracil (5-FU) therapy.
Main Results:
- The primary toxicity observed was mild leg twitching in patients receiving the 6-hour infusion.
- One patient experienced deep venous thrombosis, and a mild increase in fibrinogen levels was noted in several participants.
- No objective clinical responses were observed in the 11 evaluable patients.
Conclusions:
- rPF4 was found to be well-tolerated at the tested doses and infusion schedules.
- The study did not observe any clinical responses, suggesting limited efficacy in this setting.
- Further investigation into prolonged infusion schedules for rPF4 is warranted.