title: A pilot study of thalidomide in patients with progressive metastatic renal cell carcinoma.
abstract: BACKGROUND
  The highly vascular nature of renal cell carcinoma (RCC) suggests that angiogenesis inhibition may be therapeutic for patients with this disease. Thalidomide inhibits basic fibroblast growth factor and vascular endothelial growth factor (VEGF)-induced angiogenesis.
  
  
  METHODS
  In a pilot study, we evaluated the safety and efficacy of escalating doses of thalidomide in patients with progressive metastatic RCC (mRCC), measurable disease, and good organ function. Patients received oral thalidomide starting at 200 mg per day and increasing by 100-200 mg per day weekly until a target dose of 1200 mg per day was reached. Study endpoints were objective tumor response and toxicity.
  
  
  RESULTS
  Of the 20 patients enrolled, 19 were evaluable for response. Eighteen achieved the target dose. The most common, but reversible, toxicities were constipation, somnolence, and fatigue. Peripheral neuropathy was seen after prolonged therapy, necessitating dose reduction. Two patients achieved a partial response and nine had stable disease for a median of 14 months (range, 3-17 months). Median time to progression was 4.7 months (range, 0.7-31.3 months). Fifteen patients died (median survival, 18.1 months; 95% lower confidence bound 10.7). Survival was significantly longer in patients with higher hemoglobin level and longer time from first metastasis to start of thalidomide, but significantly shorter in patients with multiple organ involvement and previous treatments.
  
  
  CONCLUSIONS
  Thalidomide at this dose is associated with manageable acute toxicities but long-term dose-limiting neuropathy. Objective responses are rare in patients with mRCC and are characterized by delay in achieving maximum tumor reduction. Prolonged stable disease is seen in some patients, but the benefit of thalidomide, as well as other angiogenesis inhibitors, in that setting needs to be studied in controlled, randomized trials.
authors.affiliation: Department of Genitourinary Medical Oncology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ddaliani@notes.mdacc.org
authors.forename: Danai D
authors.initials: DD
authors.lastname: Daliani
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thall
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Cherie
authors.initials: C
authors.lastname: Perez
authors.forename: Rose
authors.initials: R
authors.lastname: Oliva
authors.forename: Lance
authors.initials: L
authors.lastname: Pagliaro
authors.forename: Robert
authors.initials: R
authors.lastname: Amato
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D007376:Interleukin-2; D013792:Thalidomide