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

Mark J. Ratain, Tim Eisen, Walter M. Stadler, Keith T. Flaherty, Stan B. Kaye, Gary Rosner, Martin Gore, Apurva A. Desai, Amita Patnaik, Henry Q. Xiong, Eric Rowinsky, James L. Abbruzzese, Chenghua Xia, Ronit Simantov, Brian Schwartz, Peter J. O'Dwyer

Research output: Contribution to journalArticle

Abstract

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 ≥ 25% tumor shrinkage continued open-label sorafenib; patients with ≥ 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 ≥ 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.

Original languageEnglish (US)
Pages (from-to)2505-2512
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number16
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

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Renal Cell Carcinoma
Randomized Controlled Trials
Placebos
Neoplasms
sorafenib
Disease-Free Survival
Growth
Random Allocation
Exanthema
Fatigue
Foot
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. / Ratain, Mark J.; Eisen, Tim; Stadler, Walter M.; Flaherty, Keith T.; Kaye, Stan B.; Rosner, Gary; Gore, Martin; Desai, Apurva A.; Patnaik, Amita; Xiong, Henry Q.; Rowinsky, Eric; Abbruzzese, James L.; Xia, Chenghua; Simantov, Ronit; Schwartz, Brian; O'Dwyer, Peter J.

In: Journal of Clinical Oncology, Vol. 24, No. 16, 01.06.2006, p. 2505-2512.

Research output: Contribution to journalArticle

Ratain, MJ, Eisen, T, Stadler, WM, Flaherty, KT, Kaye, SB, Rosner, G, Gore, M, Desai, AA, Patnaik, A, Xiong, HQ, Rowinsky, E, Abbruzzese, JL, Xia, C, Simantov, R, Schwartz, B & O'Dwyer, PJ 2006, 'Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma', Journal of Clinical Oncology, vol. 24, no. 16, pp. 2505-2512. https://doi.org/10.1200/JCO.2005.03.6723
Ratain, Mark J. ; Eisen, Tim ; Stadler, Walter M. ; Flaherty, Keith T. ; Kaye, Stan B. ; Rosner, Gary ; Gore, Martin ; Desai, Apurva A. ; Patnaik, Amita ; Xiong, Henry Q. ; Rowinsky, Eric ; Abbruzzese, James L. ; Xia, Chenghua ; Simantov, Ronit ; Schwartz, Brian ; O'Dwyer, Peter J. / Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 16. pp. 2505-2512.
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abstract = "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 ≥ 25{\%} tumor shrinkage continued open-label sorafenib; patients with ≥ 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 ≥ 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.",
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AU - Ratain, Mark J.

AU - Eisen, Tim

AU - Stadler, Walter M.

AU - Flaherty, Keith T.

AU - Kaye, Stan B.

AU - Rosner, Gary

AU - Gore, Martin

AU - Desai, Apurva A.

AU - Patnaik, Amita

AU - Xiong, Henry Q.

AU - Rowinsky, Eric

AU - Abbruzzese, James L.

AU - Xia, Chenghua

AU - Simantov, Ronit

AU - Schwartz, Brian

AU - O'Dwyer, Peter J.

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N2 - 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 ≥ 25% tumor shrinkage continued open-label sorafenib; patients with ≥ 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 ≥ 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.

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