Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis.
OBJECTIVE
To further investigate the effect of sunitinib, which is currently a standard of care for the treatment of metastatic renal cell carcinoma (mRCC), in patients with severe renal impairment or those undergoing dialysis.


METHODS
Clinical databases were used to identify all patients with mRCC treated with sunitinib in seven institutions internationally. Databases were searched to identify only those patients with an estimated glomerular filtration rate of < 30 mL/min/1.73 m² or those who had end-stage renal disease requiring dialysis. Baseline characteristics, adverse event data, response and progression-free survival were recorded.


RESULTS
Nineteen patients met the inclusion criteria, 10 of whom were undergoing haemodialysis. Of the nine non-dialysis-dependent patients at drug initiation, the median estimated glomerular filtration rate was 27 mL/min/1.73 m² (range 23-29). Baseline characteristics included a median age of 61 years (range 44-77); 17 patients had a Karnofsky performance status of >80; eight patients had more than two metastatic sites and 17 had undergone prior nephrectomy. The estimated median progression-free survival of this cohort was 43 weeks (range 7 to 158+) and progression has not yet been reached in six patients. Partial response or stable disease was observed as best response in 15 patients. The most common treatment-related adverse events included fatigue, diarrhoea, hand-foot skin reaction (HFSR), nausea and vomiting and rash. Grade three treatment-related adverse events including fatigue (seven patients), HFSR (two patients), diarrhoea (one patient), rash (one patient) and stomatitis (one patient) occurred in a total of 12 patients. Only one patient experienced a grade four adverse event (HFSR). Only diarrhoea (P = 0.0002), HFSR (P < 0.0001) and neutropenia (P = 0.001) were more common in patients undergoing haemodialysis compared with non-dialysis-dependent patients. Four of the non-dialysis dependent patients started at a dose of 50 mg compared with three of the patients undergoing haemodialysis. However five and two of the patients undergoing haemodialysis started at doses of 37.5 mg and 25 mg daily, respectively, compared with four and one of the non-dialysis-dependent patients. All patients took sunitinib for 4 out of every 6 weeks. Dose reductions during treatment were performed in eight patients but only one patient required discontinuation of treatment.


CONCLUSIONS
These data suggest that patients with severe renal impairment or end-stage renal disease on haemodialysis can be safely treated with sunitinib at doses of 25-50 mg daily for 4 weeks followed by a 2-week break. The observed efficacy of therapy is similar to that reported in patients with normal renal function. These preliminary results warrant confirmation in a larger cohort of patients.
Guy's and St Thomas' Hospital, London, UK.
Debra
D
Josephs
Thomas E
TE
Hutson
Charles L
CL
Cowey
Lisa M
LM
Pickering
James M
JM
Larkin
Martin E
ME
Gore
Mieke
M
Van Hemelrijck
David F
DF
McDermott
Thomas
T
Powles
Paramit
P
Chowdhury
Chris
C
Karapetis
Peter G
PG
Harper
Toni K
TK
Choueiri
Simon
S
Chowdhury
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018572:Disease-Free Survival; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D006435:Renal Dialysis; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib