in the setting of metastatic renal cell carcinoma ( mrcc ) , recent advances in the molecular understanding of oncogenic pathways have led to the development of new therapeutic strategies using targeted therapies in an adjuvant setting . sunitinib is an orally administered inhibitor of tyrosine kinases that targets the vascular endothelial and the platelet - derived growth factor receptors ( pdgfrs ) . food and drug administration , currently serves as the standard management of mrcc patients on the basis of data from phase iii trials . however , those trials excluded patients with chronic renal failure who were undergoing dialysis . recently , the sunitinib tolerance and oncologic outcomes of dialysis patients have been explored in several case series [ 2 - 5 ] . the appropriate dose of and dosing schedule for sunitinib have yet to be established in mrcc patients on hemodialysis . in addition , neither long - term treatment outcomes nor the tolerability of sunitinib has been explored in such patients . here , we report on two patients treated with sunitinib during hemodialysis and the safety issues and oncologic outcomes that we noted . a 57-year - old man underwent right radical and left partial nephrectomy to treat stage iii ( pt3n0m0 ) and stage ii papillary rcc ( pt2n0m0 ) , respectively , in january 2007 . thereafter , his renal function became impaired ; his blood urea nitrogen level was 88 mg / ml and his creatinine level was 8.5 mg / ml . hemodialysis was commenced , three times a week , in may 2007 . he also developed additional lymph node metastases in the retroperitoneum and multiple lesions in the liver . his prognostic risk category was high , as defined by the memorial sloan - kettering cancer center ( mskcc ) risk model , with a karnofsky performance status of 70% , a serum hemoglobin level of 12.1 mg / ml , a serum - corrected calcium level of 10.7 mg / ml , and a serum lactate dehydrogenase ( ldh ) concentration of 568 u / l . twenty - five milligrams of sunitinib was administered orally , on a daily basis , for 4 weeks of every 6 , commencing in july 2010 . several toxicities , including facial edema , yellowish skin pigmentation , mucositis , hypertension , and general weakness , were manageable ( grades 1 - 2 ) . however , no attempt was made to increase the dose because of a gradual increase in anemia ( from grades 1 - 4 ) associated with a requirement for frequent packed red blood cell infusion and increasingly problematic chronic fatigue and general weakness . an 80-year - old female patient underwent left radical nephrectomy after a diagnosis of stage ii clear cell carcinoma of the left kidney ( pt2n0m0 ) in 2002 . the patient was put on a hemodialysis program ( three times per week ) 6 years after nephrectomy . her medical history included essential hypertension , which had been controlled with amlodipine ( 5 mg / d ) , for 10 years . in february 2009 abdominopelvic magnetic resonance imaging ( mri ) revealed a lytic lesion with dimensions of 7 cm6 cm at the sacrum . although radiotherapy was delivered to the sacrum , the patient was referred to our department for further evaluation because the lytic lesion became enlarged 8 months after radiotherapy . the prognostic risk category was intermediate , as defined by the mskcc risk model , with a karnofsky performance status of 90% , a serum hemoglobin level of 10.6 mg / ml , a serum - corrected calcium level of 9.4 mg / ml , and an ldh level of 216 u / l . twenty - five milligrams of sunitinib was prescribed daily , commencing in march 2010 . on the 15th day of treatment , acute pulmonary edema developed as a result of uncontrolled hypertension . sunitinib could not be continued , but 15 days later , mri showed that the disease was stable . she refused further oncologic treatment and 10 months after sunitinib withdrawal , she has not developed any new metastatic lesion or progressive disease in the sacrum . a 57-year - old man underwent right radical and left partial nephrectomy to treat stage iii ( pt3n0m0 ) and stage ii papillary rcc ( pt2n0m0 ) , respectively , in january 2007 . thereafter , his renal function became impaired ; his blood urea nitrogen level was 88 mg / ml and his creatinine level was 8.5 mg / ml . hemodialysis was commenced , three times a week , in may 2007 . he also developed additional lymph node metastases in the retroperitoneum and multiple lesions in the liver . his prognostic risk category was high , as defined by the memorial sloan - kettering cancer center ( mskcc ) risk model , with a karnofsky performance status of 70% , a serum hemoglobin level of 12.1 mg / ml , a serum - corrected calcium level of 10.7 mg / ml , and a serum lactate dehydrogenase ( ldh ) concentration of 568 u / l . twenty - five milligrams of sunitinib was administered orally , on a daily basis , for 4 weeks of every 6 , commencing in july 2010 . several toxicities , including facial edema , yellowish skin pigmentation , mucositis , hypertension , and general weakness , were manageable ( grades 1 - 2 ) . however , no attempt was made to increase the dose because of a gradual increase in anemia ( from grades 1 - 4 ) associated with a requirement for frequent packed red blood cell infusion and increasingly problematic chronic fatigue and general weakness . an 80-year - old female patient underwent left radical nephrectomy after a diagnosis of stage ii clear cell carcinoma of the left kidney ( pt2n0m0 ) in 2002 . the patient was put on a hemodialysis program ( three times per week ) 6 years after nephrectomy . her medical history included essential hypertension , which had been controlled with amlodipine ( 5 mg / d ) , for 10 years . in february 2009 abdominopelvic magnetic resonance imaging ( mri ) revealed a lytic lesion with dimensions of 7 cm6 cm at the sacrum . although radiotherapy was delivered to the sacrum , the patient was referred to our department for further evaluation because the lytic lesion became enlarged 8 months after radiotherapy . the prognostic risk category was intermediate , as defined by the mskcc risk model , with a karnofsky performance status of 90% , a serum hemoglobin level of 10.6 mg / ml , a serum - corrected calcium level of 9.4 mg / ml , and an ldh level of 216 u / l . twenty - five milligrams of sunitinib was prescribed daily , commencing in march 2010 . on the 15th day of treatment , sunitinib could not be continued , but 15 days later , mri showed that the disease was stable . she refused further oncologic treatment and 10 months after sunitinib withdrawal , she has not developed any new metastatic lesion or progressive disease in the sacrum . patients with rcc who have undergone nephrectomy can develop chronic renal failure and require hemodialysis more frequently than is the case in normal populations . the long - term treatment outcomes and tolerability of sunitinib in patients on hemodialysis have recently been evaluated in several case series [ 2 - 5 ] . the targets of sunitinib include stem cell factor receptor ( kit ) , fms - like tyrosine kinase 3 , colony - stimulating factor receptor type 1 , glial cell line - derived neurotrophic factor receptor ( ret ) , pdgfr , fetal liver tyrosine kinase receptor 3 , and vascular endothelial growth factors 1 , 2 , and 3 . sunitinib and its principal metabolite , su12662 , are eliminated principally in the feces ; only 15% to 20% of the drug is cleared by the kidney . prior reports on patients undergoing chronic hemodialysis suggested that sunitinib treatment was usually well - tolerated when the drug was given at a dosage of 50 mg / d for 4 weeks of every 6 weeks . no pharmacokinetic data were available for our patients ; hence , we could not determine whether a change in the elimination kinetics of sunitinib might have increased drug toxicity . however , izzedine et al .   found wide interpatient variability in terms of sunitinib pharmacokinetics in two patients on hemodialysis , but no increase in toxicity was evident . it was concluded that the pharmacokinetic features were similar to those found in patients with normal renal function . however , clinicians treating such patients must closely monitor the side effects of fatigue , hypertension , and cardiac dysfunction , because these toxicities can be exaggerated if sunitinib is prescribed . similarly , hypertension is of concern in dialysis patients and affects up to 72% of such patients . follow - up data from the phase iii clinical trial of sunitinib ( compared to -interferon ) suggested that 21% of patients will develop a left ventricular ejection fraction ( lvef ) less than the lower limit of normal . furthermore , changes in electrocardiographic readings , elevations in cardiac enzyme ( creatine kinase - myoglobin and troponin t ) levels , and echocardiographic abnormalities ( reduced lvef and impaired contraction / relaxation ) have been documented in such patients . in addition , cardiovascular mortality in patients undergoing dialysis is much higher than that of the general public . our patients did not tolerate sunitinib well at a dose of 25 mg per day on 4 weeks out of every 6 . we were unable to increase the dose to a level higher than that given initially . thus , sunitinib may not be effective in mrcc patients who are being treated with chronic hemodialysis . in conclusion , we have described the reactions of two dialysis patients to sunitinib treatment for mrcc . contrary to recent reports indicating that sunitinib is an effective drug with manageable toxicity in the treatment of patients on chronic hemodialysis , our results indicate that sunitinib may not be well - tolerated in such patients , despite the fact that therapy was commenced with a low daily dose in those undergoing hemodialysis . it is thus important to determine a dose that is both effective and that causes minimal toxicity . , more extensive collaboration between oncologists and nephrologists is essential to ensure patient safety ; future research efforts should focus on this area .
sunitinib is a multiple tyrosine kinase receptor inhibitor that is approved for the treatment of metastatic renal cell carcinoma ( rcc ) . 
 however , neither an appropriate dose nor dosing schedule of sunitinib has yet been established for patients with metastatic rcc who are on hemodialysis . here 
 , we report on two hemodialysis patients who received sunitinib to treat metastatic rcc . 
 sunitinib was planned to be administered at a dosage of 25 mg / d for 4 of every 6 weeks . 
 although sunitinib toxicity was manageable in one patient , disease progression occurred after 4 months of treatment . in the second patient , acute pulmonary edema , caused by uncontrolled hypertension , developed on the 15th day of sunitinib therapy and 
 the drug had to be discontinued . 
 sunitinib is thus not well tolerated in a hemodialysis setting . 
 close monitoring of toxicity and dose manipulation may be required if such therapy is attempted .