title: Phase I trial of metastatic renal cell carcinoma with oral capecitabine and thalidomide.
abstract: BACKGROUND
  The highly vascular nature of renal carcinoma cells suggests that inhibition of angiogenesis may be beneficial in this disease. Thalidomide has been described as inhibitor of the fibroblast growth factor (FGF) and the vascular endothelial growth factor (VEGF). Therefore and in consideration of the promising response rates of the combination of IL-2, IFN-alpha and 5-FU [1] in metastatic renal cancer, we found it reasonable to test the combination of 5-FU and thalidomide. Thus, we conducted a phase I trial to determine safety, side effects and responses to such a treatment.
  
  
  METHODS
  Patients with metastasized renal cell cancer after nephrectomy and progress after IL-2 and interferon treatment, received oral 5-FU at a dose of 1250 mg/qm(2) twice a day for two weeks, then after pausing a week, the oral application was restarted. In addition, oral thalidomide was applied constantly at a maximum dose of 400 mg/d. The combined therapy was given for three months. The primary endpoint was duration until disease progression, the secondary endpoint the response to treatment. Response was determined by CT scans three months after the end of treatment.
  
  
  RESULTS
  In total, 12 male patients participated in the trial and received the combined oral therapy. Concerning clinical response, one mixed response (8%), a stable disease in 4/12 patients (33%) and progression was seen in 7 patients (58%). The survival from the start of the therapy showed a median of 21 months with three patients being alive. At present, the longest survival after the therapy is 51 months.
  
  
  CONCLUSIONS
  The combination of oral 5-FU and thalidomide showed clinical response with tolerable side effects. Further studies will be required to assess the outcome of this treatment regimen.
authors.affiliation: Department of Internal Medicine III, University of Bonn, Bonn, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kraemer
authors.forename: Stefan
authors.initials: S
authors.lastname: Hauser
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.forename: Marcus
authors.initials: M
authors.lastname: Gorschlüter
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
mesh_terms: D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality / Q000556:secondary*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011355:Prodrugs; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D011355:Prodrugs; D003841:Deoxycytidine; D013792:Thalidomide; D000069287:Capecitabine; D005472:Fluorouracil
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