TY - JOUR
T1 - Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor
AU - Sato, Takami
AU - Eschelman, David J.
AU - Gonsalves, Carin F.
AU - Terai, Mizue
AU - Chervoneva, Inna
AU - McCue, Peter A.
AU - Shields, Jerry A.
AU - Shields, Carol L.
AU - Yamamoto, Akira
AU - Berd, David
AU - Mastrangelo, Michael J.
AU - Sullivan, Kevin L.
PY - 2008/11/20
Y1 - 2008/11/20
N2 - Purpose: We conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma. Patients and Methods: Thirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 μg) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored. Results: MTD was not reached up to the dose level of 2,000 μg, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (≥ 1,500 μg), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites. Conclusion: Immunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.
AB - Purpose: We conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma. Patients and Methods: Thirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 μg) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored. Results: MTD was not reached up to the dose level of 2,000 μg, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (≥ 1,500 μg), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites. Conclusion: Immunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.
UR - http://www.scopus.com/inward/record.url?scp=56749158015&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000261199500021&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1200/JCO.2008.16.0705
DO - 10.1200/JCO.2008.16.0705
M3 - Article
C2 - 18838710
SN - 0732-183X
VL - 26
SP - 5436
EP - 5442
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 33
ER -