Immunoembolization of malignant liver tumor with granulocyte/macrophage colony stimulating factor (GM-CSF) and ethiodized oil followed by gelatin sponge pledgets: The final results of phase I/IIa study

Abstract

2514 Background We have developed a novel treatment approach for liver tumors: Immunoembolization with GM-CSF. In this approach, liver tumors are embolized with gelatin sponge particles after infusing a mixture of ethiodized oil and recombinant human GM-CSF (Leukine, Berlex Laboratories). A phase I/IIa study was conducted to investigate the safety and effectiveness of this treatment. Methods Patients with surgically unresectable malignant liver tumors were enrolled. The treatments were given every four weeks until maximum clinical benefit. Toxicity was assessed using the WHO criteria. The primary endpoint included dose limiting toxicity and maximum tolerated dose (MTD). Various dose levels of GM-CSF (25 mcg-2,000 mcg) were tested. Results In 39 patients with liver tumors (34 uveal melanoma, 4 skin melanoma, 1 hepatocellular carcinoma), there was no substantive toxicity observed up to the 1,000 mcg dose level. One of 6 patients at the 1,500 mcg dose level and 2 of 10 patients at the 2,000 mcg dose level developed grade 3/4 toxicity (transient elevation of alkaline phosphatase, n=1; significant liver pain, n=2; acute respiratory failure related to narcotics, n=1). There were no treatment-related deaths and MTD was not reached up to the dose level of 2,000 mcg. Subset analyses on uveal melanoma patients demonstrated 9 PR and 12 SD in 31 evaluable patients. With median follow-up of 29.8 months, the median overall survival of “intent to treat” patients was 14.5 months (range 1.5–42.6 months) and the projected one-year survival rate was 61.4% (CI 43.0–79.7%). In 3 of 6 patients whose extra-hepatic metastases were removed after immunoembolization, significant inflammatory changes were found in remote metastases. Conclusions Immunoembolization with GM-CSF is a safe and feasible approach. Encouraging preliminary results in metastatic uveal melanoma patients warrants a further clinical study for this disease. No significant financial relationships to disclose.