Sequential therapy with sorafenib and sunitinib in renal cell carcinoma
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.
- SourceAvailable from: Desmond Yip
Emerging Research and Treatments in Renal Cell Carcinoma, 02/2012; , ISBN: 978-953-51-0022-5
- "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. "
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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   . On the basis of our results, it may be that these patients might have also responded to sorafenib again. "
ABSTRACT: Acquired resistance to antiangiogenic drugs, such as sorafenib, is a major clinical problem. We studied development of a resistance to sorafenib in new preclinical models of human hepatocellular carcinoma (HCC) along with a strategy to delay such resistance--combination with metronomic chemotherapy. Three different xenograft models were studied using human Hep3B HCC cells, which are highly responsive to sorafenib, namely, orthotopic and subcutaneous transplant in severe combined immunodeficient mice, and an orthotopic transplant in nude mice. The complementary DNA for the β-subunit of human choriogonadotropin was transfected into HCC cells, and urine levels of the protein were monitored as a surrogate of tumor burden. Extended daily treatments, sometimes interrupted by a break period of 3 to 7 days to allow recovery from toxicity at sorafenib doses of 30 to 60 mg/kg, were maintained until and after evidence of tumor relapse. Initially responsive tumors seemed to develop a resistance-like phenotype after long-term daily treatment (e.g., >42 days) at doses of 30 to 60 mg/kg. Transplantation of cell lines established from progressing tumors into new hosts showed that the resistant phenotype was not propagated. Furthermore, a regimen of daily metronomic uracil + tegafur (UFT, an oral 5-fluorouracil prodrug) chemotherapy with a less toxic regimen of sorafenib (15 mg/kg per day) significantly delayed the onset of resistance (>91 days). In conclusion, development of a resistance-like phenotype to sorafenib is reversible, and metronomic UFT plus sorafenib may be a promising and well-tolerated treatment for increasing efficacy by delaying emergence of such resistance.Neoplasia (New York, N.Y.) 11/2010; 12(11):928-40. DOI:10.1593/neo.10804 · 5.40 Impact Factor
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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.Oncology Reviews 12/2011; 4(1):1-3. DOI:10.1007/s12156-010-0039-y