Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis
Authors: Josephs Debra , Hutson Thomas E. , Cowey Charles L. , Pickering Lisa M. , Larkin James M. , Gore Martin E. , Van Hemelrijck Mieke , McDermott David F. , Powles Thomas , Chowdhury Paramit , Karapetis Chris , Harper Peter G. , Choueiri Toni K. , Chowdhury Simon 
Published: January 2011

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

Sunitinib is approved for the first‐ and second‐line treatment of advanced renal cell carcinoma (RCC). Chronic kidney disease is commonly seen in patients with RCC, but knowledge regarding the effect of sunitinib in patients with severe renal impairment or on haemodialysis is limited.

In this study we define the toxicity profile and clinical outcomes of a patient cohort with RCC with severe renal impairment, or on haemodialysis who were treated with sunitinib. This retrospective study suggests that these patients can be safely treated with sunitinib at the standard dose, and the observed efficacy of therapy is similar to that reported in patients with normal renal function.

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.

PATIENTS AND 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.

CONCLUSION

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.