Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor.
OBJECTIVE
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.


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 microg) 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 microg, 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 (> or = 1,500 microg), 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.


CONCLUSIONS
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.
Sato
Takami
T
Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA. t_sato@mail.jci.tju.edu
Eschelman
David J
DJ
Gonsalves
Carin F
CF
Terai
Mizue
M
Chervoneva
Inna
I
McCue
Peter A
PA
Shields
Jerry A
JA
Shields
Carol L
CL
Yamamoto
Akira
A
Berd
David
D
Mastrangelo
Michael J
MJ
Sullivan
Kevin L
KL
D000328:Adult; D000368:Aged; D016461:Chemoembolization, Therapeutic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006499:Hepatic Artery; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000098:blood supply / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014604:Uveal Neoplasms / Q000473:pathology*
D007155:Immunologic Factors; D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor