title: Phase II trial of combination interferon-alpha and thalidomide as first-line therapy in metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To present the results of a Phase II trial of thalidomide and interferon-alpha in renal cell carcinoma.
  
  
  METHODS
  Patients with metastatic clear cell renal cell carcinoma and no prior systemic therapy were accrued. Interferon-alpha was administered at 5 million units subcutaneously three times per week. Thalidomide was started at 100 mg/day for 2 weeks and then escalated 200 mg every 2 weeks to 1000 mg or until grade 3-4 toxicity developed. Patients were assessed radiographically at baseline and after 12 weeks. Steady-state thalidomide plasma concentrations were determined.
  
  
  RESULTS
  Thirty patients were enrolled. The median age was 62 years. Seventeen patients (57%) had undergone nephrectomy before therapy. One patient died during therapy. Of the 30 patients, 29 had at least grade 2 toxicity and 17 patients had at least grade 3. At 12 weeks, no patient had a complete response, 2 had a partial response (6.7%), 8 had stable disease (26.7%), and 11 (including 1 patient with an initial partial response) had disease progression (36.7%). Nine patients were removed from the study before 12 weeks. The median follow-up was 49.6 weeks (range 2.4 to 123.7). The median time of participation in the study was 11.1 weeks (range 1.4 to 63.9). At last follow-up, 2 patients were receiving the study therapy, 1 with stable disease at 64 weeks and 1 with a partial response at 53 weeks. The median survival was 68 weeks. A linear relationship was found between the thalidomide plasma concentration and dose. No relationship was apparent between the concentration and either treatment-related toxicity or response.
  
  
  CONCLUSIONS
  Interferon-alpha and thalidomide as front-line therapy for metastatic renal cell carcinoma showed limited activity. The objective response rate was 7%. One third of patients experienced toxicity that required discontinuation of thalidomide. Randomized controlled studies are needed to determine any objective benefit of this regimen over either drug alone.
authors.affiliation: Department of Urology, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.forename: M Craig
authors.initials: MC
authors.lastname: Hall
authors.forename: Antonius
authors.initials: A
authors.lastname: Miller
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Ridenhour
authors.forename: Diana
authors.initials: D
authors.lastname: Stindt
authors.forename: James F
authors.initials: JF
authors.lastname: Lovato
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Patton
authors.forename: William
authors.initials: W
authors.lastname: Brinkley
authors.forename: Sarab
authors.initials: S
authors.lastname: Das
authors.forename: Frank M
authors.initials: FM
authors.lastname: Torti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage* / Q000097:blood
chemical_list: D016898:Interferon-alpha; D013792:Thalidomide