title: A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate.
abstract: BACKGROUND
  Current treatment for metastatic renal cell cancer with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided improved overall survival, but complete responses are rare. We conducted a multicenter phase II study to evaluate the objective response rate of 2-methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients with metastatic renal cell carcinoma who have progressed on sunitinib alone.
  
  
  METHODS
  Adults with metastatic kidney cancer were stratified depending on whether they were still taking sunitinib or had discontinued sunitinib therapy at the time of registration. Patients were treated with 2ME2 NCD alone or in combination with sunitinib. The primary endpoint was objective response rate.
  
  
  RESULTS
  In total, 17 patients were enrolled, and 12 were evaluable for response (arm A, n = 7; arm b, n = 5). In arm A, four patients had the best response of stable disease, and three patients developed disease progression. In arm B, three patients had a best response of stable disease, and two patients had disease progression. One patient continued to receive treatment for a total of 14 cycles before developing disease progression. Fatigue was the most common observed toxicities. Thirty five percent of patients required discontinuation of therapy secondary to toxicities.
  
  
  CONCLUSIONS
  2ME2 NCD had minimal anti-tumor activity, with no observed objective responses. The study was terminated because 2ME2 NCD was not found to be tolerable at the recommended phase 2 dose in this patient population. A newer 2ME2 analog is in development with a more favorable toxicity profile and increased potency.
authors.affiliation: Section of Hematology/Oncology, University of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research, Room 7105, 1111 Highland Avenue, Madison, WI 53705, USA. jybruce@medicine.wisc.edu
authors.forename: Justine Yang
authors.initials: JY
authors.lastname: Bruce
authors.forename: Jens
authors.initials: J
authors.lastname: Eickhoff
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Theodore
authors.initials: T
authors.lastname: Logan
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
authors.forename: Jamie
authors.initials: J
authors.lastname: Arnott
authors.forename: Anthony
authors.initials: A
authors.lastname: Treston
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
mesh_terms: D000077584:2-Methoxyestradiol; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D003102:Colloids; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D011758:Pyrroles / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077210:Sunitinib; D016019:Survival Analysis; D017211:Treatment Failure; D014481:United States
chemical_list: D020533:Angiogenesis Inhibitors; D003102:Colloids; D007211:Indoles; D011758:Pyrroles; D004958:Estradiol; D000077584:2-Methoxyestradiol; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib