title: Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases.
abstract: OBJECTIVE
  To investigate the effects of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis.
  
  
  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.
authors: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Matias E
authors: ME
authors: Valsecchi
authors: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Mizue
authors: M
authors: Terai
authors: Department of Radiology, Division of Interventional Radiology, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: David J
authors: DJ
authors: Eschelman
authors: Department of Radiology, Division of Interventional Radiology, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Carin F
authors: CF
authors: Gonsalves
authors: Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Inna
authors: I
authors: Chervoneva
authors: Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Jerry A
authors: JA
authors: Shields
authors: Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Carol L
authors: CL
authors: Shields
authors: Department of Radiology, Graduate School of Medicine, Osaka City University, Osaka. Japan.
authors: Akira
authors: A
authors: Yamamoto
authors: Fresenius Vascular Care, Decatur, Georgia.
authors: Kevin L
authors: KL
authors: Sullivan
authors: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: MaryAnn
authors: M
authors: Laudadio
authors: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: David
authors: D
authors: Berd
authors: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107.
authors: Michael J
authors: MJ
authors: Mastrangelo
authors: Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, 1015 Walnut St., Suite 1024, Philadelphia, PA 19107. Electronic address: takami.sato@jefferson.edu.
authors: Takami
authors: T
authors: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004311:Double-Blind Method; D004998:Ethiodized Oil / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006490:Hemostatics / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000628:therapy
chemical_list: D006490:Hemostatics; D004998:Ethiodized Oil; D016178:Granulocyte-Macrophage Colony-Stimulating Factor