Prospective Comparison of Sorafenib and Sunitinib for Second-Line Treatment of Cytokine-Refractory Kidney Cancer Patients
Department of Urology, University of Münster, Münster, Germany. Oncology
(Impact Factor: 2.42).
02/2008; 74(3-4):216-22. DOI: 10.1159/000151369
It was the aim of this study to investigate the clinical differences between the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib as second-line treatment for cytokine-refractory kidney cancer patients.
Twenty consecutive patients received continuous treatment of oral sorafenib at a dose of 400 mg twice daily in 6-week cycles. Sunitinib was administered to the remaining 20 patients at 50 mg once daily in repeated 6-week cycles consisting of daily therapy for 4 weeks, followed by a 2-week off-treatment period. We correlated best treatment responses and progression-free survival (PFS) with either TKI treatment. Adverse events were evaluated and differences were compared between both treatment groups.
In the sorafenib group, 2 (10%) patients showed a partial response (PR) and 4 (20%) patients had progressive disease (PD) versus 6 (30%) PRs and 3 (15%) PDs in the sunitinib group, respectively (p = 0.195). The median PFS was 6.4 months for sorafenib and 7.4 months for sunitinib (p = 0.969). In contrast to gender, age and the number of prior cytokine therapy cycles, the Eastern Cooperative Oncology Group performance status (p = 0.024) and the Memorial Sloan-Kettering Cancer Center risk groups for second-line treatments (p = 0.015) were independent predictive parameters of PFS. Gastrointestinal symptoms were found to occur with greater frequency in the sunitinib group (p = 0.03).
Both TKIs showed comparable clinical benefits. The Eastern Cooperative Oncology Group performance status and the Memorial Sloan-Kettering Cancer Center risk groups can help determine which patients might benefit from alternative drug treatments.
Available from: umassd.edu
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ABSTRACT: The estimation of the time-varying IF Ω(t) and amplitude
A(t) of harmonic signals is considered. The nonparametric local
polynomial approximation (LPA) is used in order to develop two new
estimators, which enable one to estimate Ω(t), Ω<sup>(1)
</sup>(t), ..., Ω((m<sub>ω</sub>-1))(t) and A(t), A<sup>(1)
</sup>(t), ..., A((m<sub>A</sub>))(t), where m<sub>ω</sub> and m
<sub>A</sub> are the degrees of the LPA of the phase and the amplitude.
The a priori amplitude information about Ω(t), A(t) and their
derivatives can be incorporated in order to improve the estimates. The
estimators of the IF and the amplitude have forms of generalized
periodograms and Fourier transforms respectively, where a polynomial
function appears in the degree of the complex exponent usual for the
Fourier transform. The asymptotic bias and covariance are obtained for
the new estimators. In particular, it is shown that one of the new
estimators ensures complete compensation of the disturbing influence of
the time-varying amplitude for the estimation of the IF and vice versa
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ABSTRACT: Summary form only given. Experimental investigations of an electric dipole surrounded with a magnetized plasma shell show that the antenna system can be matched with a feeding line in a wide frequency range near the lower-hybrid frequency. As a result, in the presence of the plasma shell the power radiated by the antenna grew by almost three orders as compared to radiation of the dipole without plasma. It has been shown that the input antenna reactance vanishes to zero at some resonant density of the plasma shell. The antenna has an inductive input reactance at higher plasma densities and a capacitive reactance at lower densities. The field structure inside the plasma shell and in the near zone of the antenna has been extensively investigated. It has been shown that the antenna radiates both as electric and magnetic dipoles. Nonlinear effects in the plasma shell have been studied. It is shown that when increasing the high-frequency power the matching is shifted in dense plasma. The experimental results have been qualitatively interpreted in the framework of an idealized model of the slow mode of a magnetized plasma cylinder. The obtained experimental results are promising for making compact low frequency antennas
Available from: Jun-Yan Liu
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ABSTRACT: The advent of multikinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor has revolutionized the treatment of highly angiogenic malignancies such as renal cell carcinoma. Interestingly, several such inhibitors are commercially available, and they each possess diverse specific beneficial and adverse effect profiles. In examining the structure of sorafenib, it was hypothesized that this compound would possess inhibitory effects on the soluble epoxide hydrolase, an enzyme with pleiotropic effects on inflammation and vascular disease. We now show that sorafenib but not another VEGF receptor targeted inhibitor sunitinib is a potent inhibitor of the human soluble epoxide hydrolase in vitro (K(I) = 17 +/- 4 nmol/L). Furthermore, sorafenib causes the expected in vivo shift in oxylipid profile resulting from soluble epoxide hydrolase inhibition, evidence of a reduction in the acute inflammatory response. Lipopolysaccharide-induced hypotension was reversed with sorafenib but not sunitinib treatment, suggesting that soluble epoxide hydrolase inhibition accounts for at least part of the anti-inflammatory effect of sorafenib. The pharmacokinetic studies presented here in light of the known potency of sorafenib as a soluble epoxide hydrolase inhibitor indicate that the soluble epoxide hydrolase will be largely inhibited at therapeutic doses of sorafenib. Thus, it is likely that soluble epoxide hydrolase inhibition contributes to the beneficial effects from the inhibition of the VEGF receptor and other kinases during treatment with sorafenib.
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