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Randomized, Placebo-Controlled, Phase III Study of First-Line Oxaliplatin-Based Chemotherapy Plus PTK787/ZK 222584, an Oral Vascular Endothelial Growth Factor Receptor Inhibitor, in Patients With Metastatic Colorectal Adenocarcinoma.
MedLine Citation:
PMID:  21464406     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE PTK787/ZK 222584 (PTK/ZK; vatalanib), an orally active, multitargeted angiogenesis inhibitor, has shown tolerability and promising activity in early-phase studies, which led to a phase III trial in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). PATIENTS AND METHODS Patients (N = 1,168) with previously untreated metastatic colorectal cancer were randomly assigned 1:1 to receive FOLFOX4 plus PTK/ZK or placebo (ClinicalTrials.gov identifier: NCT00056459). Stratification factors included WHO performance status (0 v 1 or 2) and serum lactate dehydrogenase (LDH; ≤ v > 1.5× the upper limit of normal). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR). Results PFS, OS, and ORR were not statistically improved with PTK/ZK (P > .05). Median PFS by central review was 7.7 months with PTK/ZK versus 7.6 months with placebo (hazard ratio [HR], 0.88; 95% CI, 0.74 to 1.03; P = .118); median OS was 21.4 months with PTK/ZK versus 20.5 months with placebo (HR, 1.08; 95% CI, 0.94 to 1.24; P = .260). In an exploratory post hoc analysis of PFS in patients (n = 158 per arm) with high serum LDH, a potential marker of hypoxia, PFS was longer with PTK/ZK versus placebo (7.7 v 5.8 months, respectively; HR, 0.67; 95% CI, 0.49 to 0.91; P = .009). CONCLUSION Although the efficacy objectives of this study were not met, a subgroup of patients who may potentially benefit from small-molecule vascular endothelial growth factor receptor inhibitor therapy has been identified and further research is warranted.
Authors:
J Randolph Hecht; Tanja Trarbach; John D Hainsworth; Pierre Major; Elke Jäger; Robert A Wolff; Katherine Lloyd-Salvant; György Bodoky; Kelly Pendergrass; William Berg; Bee-Lian Chen; Tarja Jalava; Gerold Meinhardt; Dirk Laurent; David Lebwohl; David Kerr
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-4
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  -     ISSN:  1527-7755     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
David Geffen School of Medicine at University of California, Los Angeles, Santa Monica, CA; Sarah Cannon Cancer Center, Nashville, TN; The University of Texas MD Anderson Cancer Center, Houston, TX; Virginia Cancer Institute, Richmond, VA; Kansas City Cancer Center, Kansas City, MO; Novartis Oncology, East Hanover, NJ; West German Cancer Center, University Hospital Essen, Essen; Medizinische Klinik II - Onkologie, Frankfurt; Bayer Schering Pharma AG, Berlin, Germany; Juravinski Cancer Centre, Hamilton, Ontario, Canada; Szent Laszlo Hospital, Budapest, Hungary; Bayer Schering Pharma Oy, Espoo, Finland; and Sidra Medical and Research Centre, Doha, Qatar.
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