PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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.
RCT Entities:
PURPOSE: 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). PATIENTS AND 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. CONCLUSION: 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: Ana M Molina; Satish K Tickoo; Nicole Ishill; Michael J Trinos; Lawrence H Schwartz; Sujata Patil; Darren R Feldman; Victor E Reuter; Paul Russo; Robert J Motzer Journal: Am J Clin Oncol Date: 2011-10 Impact factor: 2.339
Authors: Susan A J Vaziri; Dale R Grabowski; Jason Hill; Lisa R Rybicki; Robert Burk; Ronald M Bukowski; Mahrukh K Ganapathi; Ram Ganapathi Journal: Anticancer Res Date: 2009-08 Impact factor: 2.480
Authors: Simon Chowdhury; Marc R Matrana; Christopher Tsang; Bradley Atkinson; Toni K Choueiri; Nizar M Tannir Journal: Hematol Oncol Clin North Am Date: 2011-08 Impact factor: 3.722
Authors: William R Schelman; Anne M Traynor; Kyle D Holen; Jill M Kolesar; Steven Attia; Tien Hoang; Jens Eickhoff; Zhisheng Jiang; Dona Alberti; Rebecca Marnocha; Joel M Reid; Matthew M Ames; Renee M McGovern; Igor Espinoza-Delgado; John J Wright; George Wilding; Howard H Bailey Journal: Invest New Drugs Date: 2013-10-10 Impact factor: 3.850
Authors: A Z Dudek; K Lesniewski-Kmak; N J Shehadeh; O N Pandey; M Franklin; R A Kratzke; E W Greeno; P Kumar Journal: Br J Cancer Date: 2009-05-05 Impact factor: 7.640