prostate cancer is the most common cancer and the second leading cause of cancer death in men .
androgen deprivation therapy is the treatment of choice in patients with advanced metastatic disease , although progression typically occurs within 12 years of initial response [ 2 , 3 ] .
secondary hormonal therapy is an option in some patients ; however , most neoplasms ultimately progress to a situation of androgen - independent growth , namely hormone - resistant prostate cancer ( hrpc ) , androgen - independent prostate cancer or , recently , castration - resistant prostate cancer .
clinical manifestations include rising psa ( prostate serum antigen ) concentration , bone metastases , substantive pain , and soft - tissue / lymph node metastases .
some forms of hrpc treatment are systemic radiation therapy , chemotherapy , immunotherapy and estrogen therapy .
however , outcomes in hrpc are very poor and therefore novel agents are needed to improve the treatment of this condition .
many approaches , such as drugs that target specific pathways involved in cell signaling , proliferation , apoptosis , immune modulation and angiogenesis , are currently under investigation to improve survival benefit .
lenalidomide is a thalidomide analog and also known as a member of the so - called immunomodulatory drugs ( imids ) with immunomodulatory and antiangiogenic properties . in preclinical studies
, lenalidomide demonstrated antitumoral activity , inhibiting hypoxia - induced factor-1 expression by endothelial cells and epithelial tumor cells , including prostate cells , and an increase in pc-3 prostate cancer cell apoptosis with monotherapy or in combination with docetaxel . using in vitro and in vivo models of prostate cancer ,
lenalidomide inhibited growth factor - induced invasion and produced synergistic effects in combination with docetaxel that slowed tumor progression .
the few published reports about the use of lenalidomide alone or in combination in hrpc patients [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] show clear evidence of its clinical antitumoral activity in this disease . in this paper , we demonstrate that lenalidomide not only has antitumoral activity but also has no associated hematologic toxicity .
in this paper , we discuss the case of a 65-year - old male patient diagnosed in august 1999 , by transurethral resection of the prostate , with a gleason 6/10 prostate adenocarcinoma .
his past medical history included renal clear cell adenocarcinoma of both kidneys and constipation treated with lactulose .
the serum psa at the time of diagnosis was elevated to 19.7 ng / ml ( normal range 0.04.0 ) .
radiotherapy and combined androgen blockade ( cab ) therapy was initiated , comprising lutein - releasing hormone analog ( zoladex ) and bicalutamide 50 mg daily ( table 1 ) .
the patient remained asymptomatic with a low psa level for 5 years ( psa nadir 0.1 ng / ml ) . in january 2008
, biochemical and bone progression was diagnosed with an increased psa of 12 ng / ml ; bone metastases were detected by bone and ct scans .
however , 3 months later , his psa rose again to 37 ng / ml . in april 2008 ,
the patient received a third hormonal therapy with cyproterone acetate for 2 months , but biochemical progression was detected with a new increase of psa to 64 ng / ml . subsequently , docetaxel - prednisone - based chemotherapy was started , but the patient 's psa level rose again after an initial drop ( 64123857 ng / ml ) ; bone and ct scans showed bone - only metastases . in october ,
second - line chemotherapy with oxaliplatin and capecitabine on a compassionate - use basis was administered , but after 3 cycles of treatment , psa level was 233 ng / ml . in november 2008 , this therapy was replaced by treatment with fulvestrant for compassionate use and , after the first month , psa level returned to 32 ng / ml . however , in march 2009 , his psa value was higher than 300 ng / ml .
sunitinib was proposed for compassionate use . after being treated for 5 months with sunitinib ( 50 mg daily on days 14 , given every 42 days )
, in august 2009 , the patient began treatment with vinblastine - adriamycin - estramustine and ketoconazole , which was discontinued after the third cycle given the clinical deterioration associated with more intense pain ( initial ps 1 ; final ps 2 ) and increased levels of serum psa ( 1,146 ng / ml ) . in october ,
a new line of treatment with lenalidomide 25 mg / day for compassionate use together with analgesic agents was administered in november 2009 .
concomitant analgesic medication for bone pain consisted of ibuprofen 600 mg/8 h , morphine sulfate 10 mg for rescue and fentanyl patches that were discontinued in january 2010 .
the patient responded well to lenalidomide therapy , psa level markedly declined to 391 ng / ml and no hematological or cutaneous adverse events were documented ; similar hemoglobin levels were maintained before and after lenalidomide treatment ( 10.411.7 g / dl ) .
the patient regained the ability to walk over 7 km daily , maintaining his lifestyle , and he improved his general performance status until april 2010 , when fentanyl patches were reintroduced and his psa level rose to 422 ng / ml . in may 2010 , an increased psa level of 893
ng / ml was accompanied by clinical worsening due to the evolution of the disease , and therapy was suspended .
after that , estracyt ( estramustine ) 140 mg/12 h was started but no response was obtained ; psa level in july 2010 was > 5,000 ng / ml , and bone and ct scans revealed lymph node , liver and lung metastases .
the progressive deterioration of the patient 's health led to hospital admission and death in october 2010 .
proliferation , angiogenesis and evasion of immune surveillance are important pathways by which hrpc progresses . based on antiangiogenic and antitumoral properties of imids ,
it has been described that lenalidomide inhibits tumor necrosis factor- production , diminishes levels of vegf and basic fibroblast growth factor , stimulates t cells and hinders angiogenesis .
the antitumoral activity of lenalidomide is approximately 5,000 times more potent than thalidomide in animal models , and , furthermore , it has the additional advantage of being associated with a better toxicity profile . in fact , preliminary studies suggest that lenalidomide may have clinical activity in patients with metastatic castration - resistant prostate cancer [ 16 , 17 ] . nevertheless , published data about the use of lenalidomide in hrpc are rare so far , particularly in chemotherapy pre - treated patients .
all of the data have shown clear evidence of antitumor activity of lenalidomide alone [ 13 , 14 ] or in combination with docetaxel [ 9 , 12 ] , paclitaxel [ 10 , 15 ] , ketoconazole   or gm - csf   in metastatic hrpc patients .
responses described in these studies are promising with regard to survival advantage . according to our experience , the patient described here , pre - treated with chemotherapy , showed favorable response to lenalidomide therapy for 5 months  improving his general health status and quality of life , even discontinuing fentanyl administration for 4 months .
it is significant to note that psa levels declined , and disease response and pain reduction during lenalidomide administration was not accompanied by any toxicity .
hematological tests did not show alteration in hemoglobin levels , and the patient did not experience cutaneous adverse effects .
this observation provides an additional benefit and suggests that lenalidomide may be an attractive drug because of its antineoplastic activity and low side effect profile .
the evolution of the disease with the appearance of metastases led to worsening of the clinical situation of the patient .
the prognosis of prostate cancer is mainly determined by the presence or absence of metastases . in our patient ,
the development of bone , lymph node , liver and lung metastases led to progressive deterioration , which is a common complication due to widespread disease expansion .
other treatments received by the patient mainly included subsequent lines of hormonal therapy , radiotherapy and chemotherapy with antineoplastic agents  standard treatments in the management of hrpc .
although reductions in psa levels were achieved for a limited period of time , successive changes of therapy were required because of relapse and disease progression .
given the need for new agents that do not bear a potentially high cost in terms of side effects in the management of hrpc patients , lenalidomide is proposed as an interesting option .
in conclusion , the present case report presents new evidence of the potential of lenalidomide to provide clinical benefits to hrpc patients because of its antitumoral activity and lack of toxicity ; the use of lenalidomide is supported in this patient population for delaying disease progression .
 hormone - resistant prostate cancer ( hrpc ) occurs when prostate cancer is no longer responsive to hormone therapy . 
 treatment options are limited , and there is a clear necessity for therapies that improve outcome . 
 preclinical and clinical evidence supports the role of the immunomodulatory agent lenalidomide in hrpc . in this paper 
 , we report that lenalidomide showed antitumoral activity in a patient with hrpc and bone metastases pre - treated with chemotherapy , decreased the psa level and improved the patient 's health status for the first 5 months . 
 it is important to emphasize that it was not associated with hematologic toxicity . 
Introduction
Case Report
Discussion
Conclusion