Article

Sequential therapy with sorafenib and sunitinib in renal cell carcinoma

Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Cancer (Impact Factor: 4.9). 01/2009; 115(1):61-7.
Source: PubMed

ABSTRACT Sunitinib and sorafenib are small-molecule tyrosine kinase inhibitors (TKI) with antitumor activity in advanced renal cell carcinoma. A retrospective study was conducted to assess the response of renal cell carcinoma to sequential treatment with these two agents.
Tumor response was evaluated by using Response Evaluation Criteria In Solid Tumors (RECIST) criteria in patients failing first-line therapy with either sunitinib or sorafenib and subsequently receiving second-line therapy with the other TKI agent.
Twenty-nine patients received sorafenib followed by sunitinib (Group A), and 20 patients received sunitinib followed by sorafenib (Group B). TKI drugs were terminated in 6 (12%) patients in Group A and 4 (8%) in Group B because of toxicity. Median duration of stable disease for Groups A and B was 20 and 9.5 weeks, respectively. Median time from starting first TKI to disease progression after second TKI (time to progression) in Groups A and B was 78 and 37 weeks, respectively. Multivariate analysis revealed that Group B had a shorter time to progression than Group A (risk ratio [RR] 3.0; P=.016). Median overall survival was 102 and 45 weeks in Groups A and B, respectively (P=.061).
The longer duration of disease control in patients who received sorafenib followed by sunitinib warrants further investigation.

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    • "This retrospective study suggested the benefit of utilizing sorafenib as first line may improve duration of disease control if a subsequent agent is used and certainly warrants further investigation. (Dudek et al, 2009) The SWITCH trial is a prospective phase III trial which will randomize patients to upfront sunitinib and switching to sorafenib on progression versus switching from sorafenib to sunitinib on progression. The primary end point is the PFS and hopefully this trial will show further insight into which anti-VEGF treatment sequence will confer better clinical outcome in patients with metastatic RCC. "
    Emerging Research and Treatments in Renal Cell Carcinoma, 02/2012; , ISBN: 978-953-51-0022-5
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    • "One important implication of this possibility is that tumors in patients relapsing on sorafenib might respond again to the same drug after a defined break period, provided, of course, that progression of such tumors is relatively slow. There is some preliminary evidence that RCC tumors in patients who stop responding to sorafenib may respond to a later treatment of a similar drug, for example , sunitinib [2] [4] [5]. On the basis of our results, it may be that these patients might have also responded to sorafenib again. "
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    ABSTRACT: With the recent development of targeted therapies (Sorafenib, Sunitinib, Temsirolimus, Bevacizumab plus Interferon-a, Everolimus and now also Pazopanib) patients with advanced renal cell carcinoma (RCC) now have a wide range of treatment options, all of which have shown both relevant clinical activity and manageable safety profile. This abundance of active treatments, coupled with relatively limited information, we have gathered from registrative phase III trials have raised the question of how to use these agents optimally. Indeed, since presently, a cure for advanced RCC is definitely out of sight—despite the improvements made so far—the goal of therapy should be to extend progressionfree survival (PFS) while maintaining a patient’s quality of life.
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