title: Interferon alfa-2b three times daily and thalidomide in the treatment of metastatic renal cell carcinoma.
abstract: OBJECTIVE
  The antiangiogenic effect of interferon (IFN) may improve with frequent dosing and by combination with other agents with antiangiogenic activity. To evaluate this potential, we treated patients with metastatic renal cell carcinoma (RCC) with frequently dosed IFN and thalidomide.
  
  
  METHODS
  Thirty patients were given IFN-alpha-2b 0.9 MU subcutaneously three times daily for 1 month and subsequently 1.2 MU tid unless serious toxicity was encountered. Thalidomide was first given 100 mg/d for 1 week and 300 mg/d thereafter. Sera were collected before and during treatment for serum vascular endothelial growth factor (S-VEGF) analyses performed using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The intention-to-treat response rate was 20% (95% CI, 6% to 34%) and response rate for assessable patients (n = 27) was 22% (95% CI, 6% to 38%). All responses were partial. In addition, 17 patients (63%; 95% CI, 45% to 81%) had stable disease for 3 months or longer. The median time to treatment failure was 7.7 months, and median survival time was 14.9 months. The most common cause of thalidomide discontinuation was neuropathy. S-VEGF levels decreased more in patients who responded to therapy compared with those in patients whose condition had stabilized or who had progressive disease (P =.036).
  
  
  CONCLUSIONS
  The combination of frequently dosed IFN-alpha-2b and low-dose thalidomide is feasible and active in advanced RCC, but the clinical benefit may remain small compared with that of IFN alone. Results from an ongoing phase III trial comparing IFN-alpha with or without thalidomide need to be analyzed before this combination can be recommended for use outside clinical studies.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. micaela.hernberg@hus.fi
authors.forename: Micaela
authors.initials: M
authors.lastname: Hernberg
authors.forename: Pekka
authors.initials: P
authors.lastname: Virkkunen
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.forename: Henna
authors.initials: H
authors.lastname: Ahtinen
authors.forename: Hanna
authors.initials: H
authors.lastname: Mäenpää
authors.forename: Heikki
authors.initials: H
authors.lastname: joensuu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000178:diet therapy*; D008222:Lymphokines / Q000097:blood; D008297:Male; D020714:Maximum Tolerated Dose; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D015996:Survival Rate; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013792:Thalidomide