treatment of metastatic kidney cancer has changed dramatically over the past years with the use of vegf - targeted therapies and mtor inhibitors . however , resistance occurs . we report here two cases of patients who benefited from the addition of bevacizumab to temsirolimus . a 48-year - old man presented with several episodes of loss of consciousness in 2005 . the brain metastases were treated with gamma - knife radiosurgery . in 2006 , he developed lung metastases and mediastinal lymph nodes . in march 2007 , the mediastinal lymph nodes increased and he was started on sunitinib ( 50 mg 4 weeks on treatment and 2 weeks off ) . the lesions were stable but the lymphangitic infiltration was extensive and the patient still experienced dyspnoea . he improved dramatically , his oxygen consumption decreased . on the ct scan the mediastinal lymph nodes and the lymphangitic carcinomatosis lesions improved . a 54-year - old man presented with hematuria revealing a left kidney tumour in january 2004 . the pathological examination showed a pt2 clear cell carcinoma , furman grade ii tumour . in march 2005 , he progressed with liver and lung metastases and he was enrolled in the phase iii study comparing interferon to sunitinib . he had slowly progressive disease on interferon and crossed over to sunitinib in march 2006 . he had a partial response . in july 2008 , the lung and liver lesions were stable but he developed peritoneal carcinomatosis with ascitis . he was started on temsirolimus : ascitis was less abundant , the other lesions were stable . there were probably several causes to his anaemia ( a side effect of temsirolimus and the disease ) . in january 2009 , the liver lesions increased and he was started on a combination of bevacizumab ( 10 mg / kg every 2 weeks ) and temsirolimus ( 20 mg iv weekly ) . his general condition improved , the anaemia disappeared , the lesions were stable and the ascitis much less abundant . he felt that he had fewer side effects on the combination treatment than on temsirolimus alone . these two cases show the effect of adding bevacizumab to temsirolimus for patients who were progressing on the mtor inhibitor . treatment of metastatic kidney cancer has changed dramatically in the past years with the use of vegf - targeted therapies and mtor inhibitors . the vegfr tyrosine kinase inhibitor , sunitinib , is usually used in the first - line setting . another tyrosine kinase inhibitor or an mtor inhibitor can be used in the second - line setting , after progression on initial treatment . resistance to vegf pathway inhibition can be caused by upregulation of alternative pro - angiogenic factors ( fgf , angiopoietin  ) , inadequate target inhibition or enhanced receptor signalling . there are a few cases in the literature of patients who were progressing on sunitinib and who benefited from the adjunction of bevacizumab ; however , the first data show that these combinations are very toxic . this could drive upregulation of mtorc2 and further activation of akt and hif2. this could therefore lead to increase of expression of hif2 target genes , such as vegf . combining vegf - blocking agents with mtor inhibitors could contribute to reversing resistance when used in a sequential manner . however , results from the torava phase ii randomized trial show no improvement of non - progression rates with the upfront combination of bevacizumab and temsirolimus but increased toxicity leading to a high drop - out rate . there is no data in the literature on why patients should feel fewer side effects when adding bevacizumab to temsirolimus . however , some reports already mention the development of polyglobulia with anti - angiogenesis agent . this effect may correct a pre - existing anaemia [ 4 , 5 , 6 ] .
treatment of metastatic kidney cancer has changed dramatically in the past years with the use of vegf - targeted therapies and mtor inhibitors . however , resistance occurs . 
 we report here two cases of patients who benefited , both on disease control and side effects , from the addition of bevacizumab to temsirolimus , after progression on the mtor inhibitor alone .