Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases.

Matias E Valsecchi, Mizue Terai, David J Eschelman, Carin F Gonsalves, Inna Chervoneva, Jerry A Shields, Carol L Shields, Akira Yamamoto, Kevin L Sullivan, MaryAnn Laudadio, David Berd, Michael J Mastrangelo, Takami Sato

Journal: Journal of vascular and interventional radiology : JVIR 2015;26(4):523-32.e2

PMID: 25678394

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Abstract

PURPOSE

To investigate the effects of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis.

MATERIALS AND METHODS

In this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium. Fifty-two patients (immunoembolization, n = 25; BE, n = 27) were enrolled. Response was assessed after every two treatments. The primary endpoint was overall response rate (ORR) of liver metastases. Progression-free survival (PFS), overall survival (OS), and immunologic responses were secondary endpoints.

RESULTS

There were five partial responses in the immunoembolization group (ORR, 21.2%; 90% confidence interval [CI], 10.3%-30.5%) and three in the BE group (ORR, 16.7%; 90% CI, 6.3%-26.9%). Stable disease was seen in 12 patients in the immunoembolization group and 19 in the BE group. OS times were 21.5 months (95% CI, 18.5-24.8 mo) with immunoembolization and 17.2 months (95% CI, 11.9-22.4 mo) with BE. The degree of proinflammatory cytokine production was more robust after immunoembolization and correlated with time to "systemic" extrahepatic progression. In the immunoembolization group, interleukin (IL)-6 levels at 1 hour (P = .001) and IL-8 levels at 18 hours after the procedure (P < .001) were significant predictors of longer systemic PFS. Moreover, a dose-response pattern was evident between posttreatment serum cytokine concentrations and systemic PFS.

CONCLUSIONS

Immunoembolization induced more robust inflammatory responses, which correlated with the delayed progression of extrahepatic systemic metastases.

Address: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.; Department of Radiology, Division of Interventional Radiology, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.; Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.; Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.; Department of Radiology, Graduate School of Medicine, Osaka City University, Osaka. Japan.; Fresenius Vascular Care, Decatur, Georgia.; Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. Electronic address: [email protected].

DOI: 10.1016/j.jvir.2014.11.037

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MeSH Terms: Adult, Aged, Aged, 80 and over, Chemoembolization, Therapeutic, Double-Blind Method, Ethiodized Oil, Female, Granulocyte-Macrophage Colony-Stimulating Factor, Hemostatics, Humans, Liver Neoplasms, Male, Melanoma, Middle Aged, Treatment Outcome, Uveal Neoplasms