title: Phase II trial of bortezomib for patients with advanced renal cell carcinoma.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of bortezomib (Velcade; Milennium Pharmaceuticals Inc, Cambridge, MA; formerly PS-341) in patients with metastatic renal cell carcinoma (RCC).
  
  
  METHODS
  Thirty-seven patients with metastatic RCC were treated with bortezomib. The first 25 patients enrolled onto the trial were treated with a dose of 1.5 mg/m2. The dose was decreased to 1.3 mg/m2 for the subsequent 12 patients, because more than 50% of the patients treated at the higher dose required dose reductions. Bortezomib was given by intravenous administration on a twice-weekly schedule for 2 weeks followed by 1 week without treatment until progression or unacceptable toxicity occurred. Twenty-three patients (62%) previously had undergone nephrectomy, and 19 patients (51%) had previously been treated with cytokine therapy.
  
  
  RESULTS
  Of the 37 assessable patients, the best response was a partial response in four patients (11%; 95% CI, 3% to 25%) and stable disease in 14 patients (38%; 95% CI, 23% to 55%). The four patients with partial response experienced response durations of 8, 8+, 15+, and 20+ months. Grade 2 or 3 sensory neuropathy was present in 10 patients (53%) overall. One patient in the 1.5 mg/m2 group had grade 3 sensory neuropathy; no grade 3 sensory neuropathy was seen in the 1.3 mg/m2 group.
  
  
  CONCLUSIONS
  The results of this trial suggest that bortezomib has an antitumor effect in individual patients with metastatic RCC. The small proportion of patients who achieved a partial response does not support routine use in metastatic RCC. Efforts to identify the molecular profile associated with clinical response or combination therapy with interferon alfa or other novel agents, may be considered.
authors.affiliation: Genitourinary Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: G Varuni
authors.initials: GV
authors.lastname: Kondagunta
authors.forename: Beverly
authors.initials: B
authors.lastname: Drucker
authors.forename: Lawrence
authors.initials: L
authors.lastname: Schwartz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bacik
authors.forename: Stephanie
authors.initials: S
authors.lastname: Marion
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib