The Oncologist, Vol. 12, No. 2, 191-200, February 2007; doi:10.1634/theoncologist.12-2-191
© 2007 AlphaMed Press
Sorafenib and Sunitinib in the Treatment of Advanced Non-Small Cell Lung Cancer
Cesare Gridelli,
Paolo Maione,
Filomena Del Gaizo,
Giuseppe Colantuoni,
Ciro Guerriero,
Carmine Ferrara,
Dario Nicolella,
Daniela Comunale,
Alba De Vita,
Antonio Rossi
Division of Medical Oncology, "S.G. Moscati" Hospital, Avellino, Italy
Key Words. Sorafenib • Sunitinib • Targeted therapy • Multikinase inhibitors • NSCLC
Correspondence:
Cesare Gridelli, M.D., Division of Medical Oncology, "S.G. Moscati" Hospital, Contrada Amoretta, 83100 Avellino, Italy; Telephone: +39-0825-203573; Fax: +39-0825-203556; e-mail: cgridelli{at}libero.it
Despite the optimization of chemotherapy regimens, treatment outcomes for advanced non-small cell lung cancer (NSCLC) are still considered to be disappointing. Thus, clinical research of new treatment strategies is warranted. Several targeted agents have been introduced into clinical trials in NSCLC, but to date, only a few of these new agents can offer hope of a substantial impact on the natural history of the disease. One of the main reasons for the failure of several clinical trials of targeted therapy in lung cancer is that there is multilevel cross-stimulation among the targets of the new biological agents along several pathways of signal transduction that lead to neoplastic events; blocking only one of these pathways, as most first-generation targeted agents do, allows others to act as salvage or escape mechanisms for cancer cells. Sorafenib and sunitinib are two oral multitargeted receptor tyrosine kinase inhibitors. Sorafenib is a multikinase inhibitor that inhibits the kinase activity of both C-RAF and B-RAF and targets the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-ß and stem cell factor receptor [KIT]). Sunitinib is a multitargeted inhibitor of PDGFR, KIT, fms-like tyrosine kinase 3, and VEGFR. The kinases targeted and inhibited by sorafenib and sunitinib directly and indirectly regulate tumor growth, survival, and angiogenesis, and this might be expected to result in broad antitumor efficacy. Sorafenib and sunitinib have been approved by the U.S. Food and Drug Administration for the treatment of metastatic renal cell carcinoma; sunitinib has also been approved for the treatment of gastrointestinal stromal tumors. Their mechanism of action, preclinical data, and phase II studies suggest efficacy in the treatment of advanced NSCLC.
This article has been cited by other articles:

|
 |

|
 |
 
T. Donnem, S. Al-Saad, K. Al-Shibli, L.-T. Busund, and R. M. Bremnes
Co-expression of PDGF-B and VEGFR-3 strongly correlates with lymph node metastasis and poor survival in non-small-cell lung cancer
Ann. Onc.,
February 1, 2010;
21(2):
223 - 231.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Basille, M. Andrejak, H. Bentayeb, M. Kanaan, C. Fournier, E. Lecuyer, M. Boutemy, R. Garidi, Y. Douadi, and C. Dayen
Bronchial Fistula Associated with Sunitinib in a Patient Previously Treated with Radiation Therapy
Ann. Pharmacother.,
February 1, 2010;
44(2):
383 - 386.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bozec, A. Sudaka, N. Toussan, J.-L. Fischel, M.-C. Etienne-Grimaldi, and G. Milano
Combination of sunitinib, cetuximab and irradiation in an orthotopic head and neck cancer model
Ann. Onc.,
October 1, 2009;
20(10):
1703 - 1707.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. P. Morelli, A. M. Brown, T. M. Pitts, J. J. Tentler, F. Ciardiello, A. Ryan, J. M. Jurgensmeier, and S. G. Eckhardt
Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines
Mol. Cancer Ther.,
September 1, 2009;
8(9):
2546 - 2558.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Takano, N. Ishikawa, R. Nishino, K. Masuda, W. Yasui, K. Inai, H. Nishimura, H. Ito, H. Nakayama, Y. Miyagi, et al.
Identification of Nectin-4 Oncoprotein as a Diagnostic and Therapeutic Target for Lung Cancer
Cancer Res.,
August 15, 2009;
69(16):
6694 - 6703.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Lebanony, H. Benjamin, S. Gilad, M. Ezagouri, A. Dov, K. Ashkenazi, N. Gefen, S. Izraeli, G. Rechavi, H. Pass, et al.
Diagnostic Assay Based on hsa-miR-205 Expression Distinguishes Squamous From Nonsquamous Non-Small-Cell Lung Carcinoma
J. Clin. Oncol.,
April 20, 2009;
27(12):
2030 - 2037.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. A. Pennell and T. J. Lynch Jr.
Combined Inhibition of the VEGFR and EGFR Signaling Pathways in the Treatment of NSCLC
Oncologist,
April 1, 2009;
14(4):
399 - 411.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. G. CHARPIDOU, I. GKIOZOS, S. TSIMPOUKIS, D. APOSTOLAKI, K. D. DILANA, E. M. KARAPANAGIOTOU, and K. N. SYRIGOS
Therapy-induced Toxicity of the Lungs: An Overview
Anticancer Res,
February 1, 2009;
29(2):
631 - 639.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Houben, H. Voigt, C. Noelke, V. Hofmeister, J. C. Becker, and D. Schrama
MAPK-independent impairment of T-cell responses by the multikinase inhibitor sorafenib
Mol. Cancer Ther.,
February 1, 2009;
8(2):
433 - 440.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Hirata, T. Yamabuki, D. Miki, T. Ito, E. Tsuchiya, M. Fujita, M. Hosokawa, K. Chayama, Y. Nakamura, and Y. Daigo
Involvement of Epithelial Cell Transforming Sequence-2 Oncoantigen in Lung and Esophageal Cancer Progression
Clin. Cancer Res.,
January 1, 2009;
15(1):
256 - 266.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Yang, T. E. Van Meter, R. Buettner, M. Hedvat, W. Liang, C. M. Kowolik, N. Mepani, J. Mirosevich, S. Nam, M. Y. Chen, et al.
Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas
Mol. Cancer Ther.,
November 1, 2008;
7(11):
3519 - 3526.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Zanini, A. Chetta, and D. Olivieri
Review: Therapeutic perspectives in bronchial vascular remodeling in COPD
Therapeutic Advances in Respiratory Disease,
June 1, 2008;
2(3):
179 - 187.
[Abstract]
[PDF]
|
 |
|
Copyright © 2007 by AlphaMed Press.
|
|