Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.

Journal Article (Journal Article;Multicenter Study)

PURPOSE: This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with > or = 25% tumor shrinkage continued open-label sorafenib; patients with > or = 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib. RESULTS: Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity. CONCLUSION: Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.

Full Text

Duke Authors

Cited Authors

  • Ratain, MJ; Eisen, T; Stadler, WM; Flaherty, KT; Kaye, SB; Rosner, GL; Gore, M; Desai, AA; Patnaik, A; Xiong, HQ; Rowinsky, E; Abbruzzese, JL; Xia, C; Simantov, R; Schwartz, B; O'Dwyer, PJ

Published Date

  • June 1, 2006

Published In

Volume / Issue

  • 24 / 16

Start / End Page

  • 2505 - 2512

PubMed ID

  • 16636341

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2005.03.6723


  • eng

Conference Location

  • United States