Double-Blind, Randomized Trial of Docetaxel Plus Vandetanib Versus Docetaxel Plus Placebo in Platinum-Pretreated Metastatic Urothelial Cancer

被引：142

作者：

Choueiri, Toni K. ^{[1
]}

Ross, Robert W. ^{[1
]}

Jacobus, Susanna ^{[1
]}

Vaishampayan, Ulka ^{[3
]}

Yu, Evan Y. ^{[4
]}

Quinn, David I. ^{[5
]}

Hahn, Noah M. ^{[6
]}

Hutson, Thomas E. ^{[7
]}

Sonpavde, Guru ^{[8
]}

Morrissey, Stephanie C. ^{[1
]}

Buckle, Geoffrey C. ^{[1
]}

Kim, William Y. ^{[9
]}

Petrylak, Daniel P. ^{[10
]}

Ryan, Christopher W. ^{[11
]}

Eisenberger, Mario A. ^{[12
]}

Mortazavi, Amir ^{[13
,14
]}

Bubley, Glenn J. ^{[2
]}

Taplin, Mary-Ellen ^{[1
]}

Rosenberg, Jonathan E. ^{[1
]}

Kantoff, Philip W. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Boston, MA 02215 USA

[2] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[3] Karmanos Canc Inst, Detroit, MI USA

[4] Univ Washington, Seattle, WA 98195 USA

[5] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[6] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA

[7] Baylor Sammons Canc Ctr, Dallas, TX USA

[8] Baylor Coll Med, Houston, TX 77030 USA

[9] Univ N Carolina, Chapel Hill, NC USA

[10] Columbia Univ, Med Ctr, New York, NY USA

[11] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA

[12] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[13] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA

[14] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 05期

关键词：

TRANSITIONAL-CELL CARCINOMA; PHASE-II TRIAL; EPIDERMAL-GROWTH-FACTOR; ADVANCED BLADDER-CANCER; 2ND-LINE TREATMENT; PROGNOSTIC-FACTORS; PACLITAXEL; CHEMOTHERAPY; ZD1839;

D O I：

10.1200/JCO.2011.37.7002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided alpha at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. Conclusion In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal. J Clin Oncol 30: 507-512. (C) 2011 by American Society of Clinical Oncology

引用

页码：507 / 512

页数：6

共 28 条

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