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Saturday, June 03, 2006
Sorafenib (Nexaver)
個人輸入
2nd opinion
腎細胞癌 ASCO 2005
Sorafenib のJCOアブストラクト
1
それでは、発表された分子標的治療薬の臨床成績について紹介します。
まず、今回Phase Ⅲの中間成績が発表され、現在最も開発が進んでいるのがBAY 43-9006、
一般名sorafenib と言われている薬剤です。この薬剤は癌の増殖にかかわる二つの重要な要因、すなわち腫瘍細胞増殖と腫瘍血管新生に関与するキナーゼ群であるRAF、VEGFR-2、
VEGFR-3、PDGFR-β、KIT、そしてRET を標的とした経口投与薬です。
効果の評価対象となったsorafenib 群335例、プラセボ群337例でみますと、sorafenib 群でPR
２％（７例）と腫瘍縮小効果は高くはありません。しかしSD78％（261例）を加えた病勢コ
ントロール率は80％に上っています。また、今回最も注目されたのは、このような大規模の
試験で、プラセボ群のMedian PFS が12週であったのに対し、Sorafenib 群のそれは24週と、極
めて強い有意差をもってその延長効果が証明されたことです。薬剤関連有害事象としては、発疹、下痢、手足皮膚症候群、脱毛、疲労、掻痒、嘔気、高血圧などが比較的高頻度にみられましたが、グレード３と４の頻度は低く、忍容性は高いと思われました。本邦において、この薬は現在Phase Ⅱの段階にあり、その結果が大いに期待されます。
Nexavar （ネクサバール）
成分名 Sorafenib （ソラフェニブ）
適応 進行性腎細胞癌
剤型 規格・容量 包装単位 薬監証明 冷蔵輸送 製造元 出荷国 価格 納期 ご注文はこちらから
タブレット 200mg 112 必要なし 必要なし Bayer スイス 655,000円 14日-20日
Nexavar 添付文書
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 L. 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
From the University of Chicago, Chicago, IL; Royal Marsden Hospital, Surrey, United Kingdom; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; The University of Texas M.D. Anderson Cancer Center, Houston; Cancer Therapy and Research Center, San Antonio, TX; Bayer Pharmaceuticals Corporation, West Haven, CT
Address reprint requests to Mark J. Ratain, MD, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637; e-mail: mratain@medicine.bsd.uchicago.edu
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.
Supported by Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
2nd opinion
腎細胞癌 ASCO 2005
Sorafenib のJCOアブストラクト
1
それでは、発表された分子標的治療薬の臨床成績について紹介します。
まず、今回Phase Ⅲの中間成績が発表され、現在最も開発が進んでいるのがBAY 43-9006、
一般名sorafenib と言われている薬剤です。この薬剤は癌の増殖にかかわる二つの重要な要因、すなわち腫瘍細胞増殖と腫瘍血管新生に関与するキナーゼ群であるRAF、VEGFR-2、
VEGFR-3、PDGFR-β、KIT、そしてRET を標的とした経口投与薬です。
効果の評価対象となったsorafenib 群335例、プラセボ群337例でみますと、sorafenib 群でPR
２％（７例）と腫瘍縮小効果は高くはありません。しかしSD78％（261例）を加えた病勢コ
ントロール率は80％に上っています。また、今回最も注目されたのは、このような大規模の
試験で、プラセボ群のMedian PFS が12週であったのに対し、Sorafenib 群のそれは24週と、極
めて強い有意差をもってその延長効果が証明されたことです。薬剤関連有害事象としては、発疹、下痢、手足皮膚症候群、脱毛、疲労、掻痒、嘔気、高血圧などが比較的高頻度にみられましたが、グレード３と４の頻度は低く、忍容性は高いと思われました。本邦において、この薬は現在Phase Ⅱの段階にあり、その結果が大いに期待されます。
Nexavar （ネクサバール）
成分名 Sorafenib （ソラフェニブ）
適応 進行性腎細胞癌
剤型 規格・容量 包装単位 薬監証明 冷蔵輸送 製造元 出荷国 価格 納期 ご注文はこちらから
タブレット 200mg 112 必要なし 必要なし Bayer スイス 655,000円 14日-20日
Nexavar 添付文書
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 L. 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
From the University of Chicago, Chicago, IL; Royal Marsden Hospital, Surrey, United Kingdom; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; The University of Texas M.D. Anderson Cancer Center, Houston; Cancer Therapy and Research Center, San Antonio, TX; Bayer Pharmaceuticals Corporation, West Haven, CT
Address reprint requests to Mark J. Ratain, MD, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637; e-mail: mratain@medicine.bsd.uchicago.edu
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.
Supported by Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Posted by: Ds20040999 / 4:55 AM 
