Sorafenib after combination therapy with gemcitabine plus doxorubicine in patients with sarcomatoid renal cell Carcinoma: a prospective evaluation

European Journal of Medical Research

CG Stief¹  A Karl¹  M Siebels¹  M Bader¹  T Stadler¹  A Roosen¹  N Haseke¹  M Staehler¹ 

[1] Department of Urology, University of Munich, Klinikum Grosshadern, Munich, Germany

关键词: angiogenesis;    survival;    multi-kinase inhibitor;    sorafenib;    chemotherapy;    sarcomatoid;    renal cell carcinoma;   

Others  :  834459
DOI  :  10.1186/2047-783X-15-7-287

 received in 2009-11-26, accepted in 2010-01-12,  发布年份 2010

【 摘 要 】

Background

Sarcomatoid renal cell cancer (RCC) is a distinct histological variant of RCC that is associated with rapid progression and a poor prognosis. The optimal treatment for patients with sarcomatoid RCC remains to be defined. Gemcitabine plus doxorubicine (GD) has shown some efficacy, however durability of response is limited. We carried out a prospective, open-label study to investigate the efficacy and safety of sorafenib in patients after GD failure in sarcomatoid RCC.

Methods

Fifteen patients with pure sarcomatoid RCC and objective progressive disease were treated with GD (gemcitabine 1500 mg/m², doxorubicine 50 mg/m² administered by weekly intravenous infusion) until progression of disease. Subsequently 9 patients were switched to sorafenib (400 mg twice daily). Tumor response was measured by physical examination and computerized tomography scans and evaluated according to Response Evaluation Criteria in Solid Tumors criteria.

Results

Median time to progression (TTP) under GD was 6.6 months (range 0.8 - 8 months). During GD treatment there were no remissions and 6 patients died from progressive disease. Median TTP for the 9 patients switched to sorafenib was 10.9 months (range 0.6 - 25.5 months). During sorafenib therapy one patient had a partial remission lasting for 3 months and 4 patients experienced stable disease with a duration of 3 to 9 months. Four patients immediately progressed on sorafenib treatment but had a slower dynamic of tumor progression than under GD. Dosing in both treatment phases was generally well tolerated with manageable toxicities and no requirement for dose reduction.

Conclusions

Chemotherapy with GD was ineffective in our patients with pure sarcomatoid RCC. Subsequent anti-angiogenic treatment using the multi-tyrosine kinase inhibitor sorafenib resulted in additional progression-free survival in 5 of 9 patients. Further evaluation of targeted anti-angiogenic agents for the treatment of sarcomatoid RCC is warranted.

【 授权许可】

   
2010 I. Holzapfel Publishers

【 图 表 】

Figure 1.

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