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Antitumor and Antimicrovascular Effects of Nexavar
Antitumor and antimicrovascular effects of Nexavar (sorafenib) in fresh human tumor culture in comparison with other putative tyrosine kinase inhibitors (TKIs).
Sub-category:
Tyrosine Kinase Inhibitors
Category:
Developmental Therapeutics - Experimental Therapeutics
Meeting:
2010 ASCO Annual Meeting
Session Type and Session Title:
Abstract published in conjunction with the meeting.
Abstract No:
e13617
Citation:
J Clin Oncol 28, 2010 (suppl; abstr e13617)
Author(s):
L. M. Weisenthal; Weisenthal Cancer Group, Huntington Beach, CA
Abstract:
Background: Nexavar is postulated to be a clinical anti-angiogenic agent. Yet preliminary clinical evidence suggests it may not be cross resistant with other anti-angigenic agensts, including Sutent (sunitinib) (Tamaskar, et al. J Urology 179:81,2008). An alternative hypothesis is that Nexavar has direct antitumor cell effects. In order to determine whether antivascular or antitumor cell effects were more important, we measured both antivascular and antitumor cell effects of Nexavar in short term cultures of fresh human tumor biopsies and compared these activities with those of other putative tyrosine kinase inhibitors.
Methods: We used methods described in the following publication: Weisenthal, et al. Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood. J Intern Med 264: 275-287, 2008. doi: 10.1111/j.1365-2796.2008.01955.x
Results: Utilizing methods described in Table 1 of the above publication, we determined the relative antivascular activity vs antitumor cell activity of tyrosine kinase inhibitors and other agents. Expressed as a ratio of antivascular activity divided by antitumor cell activity, the rank order (greatest to least relative antivascular activity) was as follows: pazopanib > bevacizumab > dasatinib > sunitinib > erlotinib > lapatinib > gefitinib > imatinib > sorafenib > cisplatin. Antivascular activity of Nexavar was minimal. We also determined correlation coefficients for antitumor cell activity of these agents (comparing activity of two agents at a time in the same specimen datasets; size of comparison tyrosine kinase inhibitor datasets ranging from 11 to 587, median of 247 direct activity comparisons between pairs of agents. Correlation coefficients are as follows: doxorubicin/epirubicin 0.88, cisplatin/carboplatin 0.86, paclitaxel/docetaxel 0.64, cisplatin/oxaliplatin 0.48, cisplatin/5FU 0.35, gefitinib/erlotinib 0.61, erlotinib/imatinib 0.51, erlotinib/lapatinib 0.46, erlotinib/dasatinib 0.41, erlotinib/sunitinib 0.28, sunitinib/imatinib 0.51, soraf/dasatinib 0.19, soraf/gefitinib 0.17, soraf/pazopanib 0.10, soraf/sunitinib 0.01, soraf/lapatinib 0.00, soraf/imatinib -0.01.
Conclusions: Nexavar has minimal antivascular activity in short term cultures of fresh human tumors, in comparison with other tyrosine kinase inhibitors and has virtually non-cross resistant antitumor cell activity.
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