scholarly journals Sorafenib, a dual Raf kinase/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs

Oncogene ◽  
2009 ◽  
Vol 29 (8) ◽  
pp. 1190-1202 ◽  
Author(s):  
V Ramakrishnan ◽  
M Timm ◽  
J L Haug ◽  
T K Kimlinger ◽  
L E Wellik ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Raf Kinase ◽  
Endothelial Growth Factor ◽  
Receptor Inhibitor

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

2011 ◽  
Vol 29 (15) ◽  
pp. 1997-2003 ◽  
Author(s):  
J. Randolph Hecht ◽  
Tanja Trarbach ◽  
John D. Hainsworth ◽  
Pierre Major ◽  
Elke Jäger ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Angiogenesis Inhibitor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Serum Lactate Dehydrogenase ◽  
Vascular Endothelial ◽  
Potential Marker ◽  
Endothelial Growth Factor ◽  
Receptor Inhibitor

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.

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