Skip Navigation


Annals of Oncology Advance Access originally published online on May 19, 2005
Annals of Oncology 2005 16(8):1391-1397; doi:10.1093/annonc/mdi247
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
16/8/1391    most recent
mdi247v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (57)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Holden, S. N.
Right arrow Articles by Hurwitz, H. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Holden, S. N.
Right arrow Articles by Hurwitz, H. I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society for Medical Oncology

Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors

S. N. Holden1, S. G. Eckhardt1, R. Basser2, R. de Boer2, D. Rischin2, M. Green2, M. A. Rosenthal2, C. Wheeler3, A. Barge4 and H. I. Hurwitz5,*

1 University of Colorado Cancer Center, Aurora, CO, USA; 2 Cancer Trials Australia, Melbourne, Australia; 3 Astra Zeneca, Boston, MA, USA; 4 Astra Zeneca, Alderley Park, UK; 5 Duke University Medical Centre, Durham, NC, USA

* Correspondence to: Dr H. I. Hurwitz, Duke University Medical Centre, Box 3052, Durham, NC 27710, USA. Tel: +1-919-681-5257; Fax: +1-919-684-9712; Email: hurwi004{at}mc.duke.edu

Background:: ZD6474 selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor and epidermal growth factor receptor. The safety, tolerability and pharmacokinetics of ZD6474 were assessed in a phase I dose-escalation study of patients with advanced solid tumors.

Patients and methods:: Adult patients with tumors refractory to standard treatments received once-daily oral ZD6474 (50–600 mg) in 28-day cycles, until disease progression or unacceptable toxicity was observed.

Results:: Seventy-seven patients were treated at doses of 50 mg (n=9), 100 mg (n=19), 200 mg (n=8), 300 mg (n=25), 500 mg (n=8), and 600 mg (n=8). Adverse events were generally mild, and the most common dose-limiting toxicities (DLT) were diarrhea (n=4), hypertension (n=4), and rash (n=3). The incidence of most adverse events appeared to be dose-dependant. In the 500 mg/day cohort, 3/8 patients experienced DLT and this dose was therefore considered to exceed the maximum tolerated dose. Pharmacokinetic analysis confirmed that ZD6474 was suitable for once-daily oral dosing.

Conclusions:: Once-daily oral dosing of ZD6474 at 300 mg/day is generally well tolerated in patients with advanced solid tumors, and this dose is being investigated in phase II trials.

Key words: anti-angiogenesis, dose escalation, pharmacokinetics, tolerability, ZD6474


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
E. L. Bradshaw-Pierce, C. A. Steinhauer, D. Raben, and D. L. Gustafson
Pharmacokinetic-directed dosing of vandetanib and docetaxel in a mouse model of human squamous cell carcinoma
Mol. Cancer Ther., September 1, 2008; 7(9): 3006 - 3017.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Choi, D. Sano, M. Cheung, M. Zhao, S. A. Jasser, A. J. Ryan, L. Mao, W.-T. Chen, A. K. El-Naggar, and J. N. Myers
Vandetanib Inhibits Growth of Adenoid Cystic Carcinoma in an Orthotopic Nude Mouse Model
Clin. Cancer Res., August 15, 2008; 14(16): 5081 - 5089.
[Abstract] [Full Text] [PDF]

Home page
 Neuro OncolHome page
C. P. Carden, J. M.G. Larkin, and M. A. Rosenthal
What is the risk of intracranial bleeding during anti-VEGF therapy?
Neuro-oncol, August 1, 2008; 10(4): 624 - 630.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. V. Heymach, B. E. Johnson, D. Prager, E. Csada, J. Roubec, M. Pesek, I. Spasova, C. P. Belani, I. Bodrogi, S. Gadgeel, et al.
Randomized, Placebo-Controlled Phase II Study of Vandetanib Plus Docetaxel in Previously Treated Non Small-Cell Lung Cancer
J. Clin. Oncol., September 20, 2007; 25(27): 4270 - 4277.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. L. Strevel, D. J. Ing, and L. L. Siu
Molecularly Targeted Oncology Therapeutics and Prolongation of the QT Interval
J. Clin. Oncol., August 1, 2007; 25(22): 3362 - 3371.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. O. Hanrahan and J. V. Heymach
Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors Vandetanib (ZD6474) and AZD2171 in Lung Cancer
Clin. Cancer Res., August 1, 2007; 13(15): 4617s - 4622s.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
V. Johanson, H. Ahlman, P. Bernhardt, S. Jansson, L. Kolby, F. Persson, G. Stenman, C. Sward, B. Wangberg, M. Stridsberg, et al.
A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis
Endocr. Relat. Cancer, June 1, 2007; 14(2): 433 - 444.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Giaccone
The Potential of Antiangiogenic Therapy in Non-Small Cell Lung Cancer
Clin. Cancer Res., April 1, 2007; 13(7): 1961 - 1970.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
L. V. Sequist
Second-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer
Oncologist, March 1, 2007; 12(3): 325 - 330.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. L. Gustafson, E. L. Bradshaw-Pierce, A. L. Merz, and J. A. Zirrolli
Tissue Distribution and Metabolism of the Tyrosine Kinase Inhibitor ZD6474 (Zactima) in Tumor-Bearing Nude Mice following Oral Dosing
J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 872 - 880.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. V. Heymach, M. Nilsson, G. Blumenschein, V. Papadimitrakopoulou, and R. Herbst
Epidermal growth factor receptor inhibitors in development for the treatment of non-small cell lung cancer.
Clin. Cancer Res., July 15, 2006; 12(14): 4441s - 4445s.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.