Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer receiving haemodialysis: a retrospective Italian survey

Abstract

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sunitinib and sorafenib are orally administered multikinase inhibitors approved for the treatment of advanced RCC. The limited pharmacokinetics data on sunitinib and sorafenib suggest that haemodialysis does not significantly alter plasma concentrations. In this retrospective study we define the safety and efficacy of tyrosine kinase inhibitors in patients with metastatic RCC (mRCC) and end‐stage renal disease requiring haemodialysis. Even though the retrospective nature of this survey and the relatively small sample size represent major limitations, these data indicate that treatment with sunitinib and sorafenib in this cohort of patients is feasible with no unexpected toxicity and good efficacy, results similar to those in the general population of patients with mRCC. OBJECTIVE To investigate the safety and efficacy of tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) and end‐stage renal disease requiring haemodialysis (HD). PATIENTS AND METHODS Between July 2006 and December 2010, 24 patients undergoing HD were treated with sunitinib and/or sorafenib for mRCC in 14 Italian institutions. We retrospectively reviewed the medical records of these patients to evaluate the administered doses of TKIs, treatment‐related toxicities and the clinical response to therapy. RESULTS Sunitinib was administered at 50 mg daily for 4–6 weeks in six patients, 37.5 mg daily for 4–6 weeks in seven patients (one patient subsequently increased the dose to 50 mg daily), 25 mg daily for 4–6 weeks in two patients and 12.5 mg daily for 4–6 weeks in one patient. Among the eight patients treated with sorafenib, four patients received 800 mg daily (400 mg every 12 h), three patients 400 mg daily and one patient 200 mg daily with a continuous schedule. The estimated median progression‐free and overall survival periods of this cohort of patients were 10.3 months and 22.6 months, respectively. With regard to tolerability and safety, no unexpected adverse events were registered and no grade 4 haematological or non‐haematological toxicities were reported. CONCLUSIONS Sunitinib and sorafenib treatment is not contraindicated in patients with mRCC undergoing HD. The outcome of this patient population is similar to that observed in patients with normal renal function treated with TKIs. These results merit further confirmation by a larger prospective trial.

Outcomes of Patients With Metastatic Renal Cell Carcinoma and End-Stage Renal Disease Receiving Dialysis and Targeted Therapies: A Single Institution Experience

“…Outcomes compared with patients with normal kidney function were similar with a reported median progression-free survival (PFS) of 10.3 months and a median OS of 22.6 months. 9 We similarly found sunitinib and sorafenib to be well tolerated, with no Grade 4 toxicities reported. In our study, patients had a median PFS of 5.6 months with sunitinib treatment and 4.2 months with sorafenib treatment.…”

“…Masini and colleagues conducted a retrospective study of 24 patients with mRCC who were treated with sunitinib (16 patients) or sorafenib (8 patients). 9 Both TKIs appeared to be safe with no unexpected adverse outcomes noted. Outcomes compared with patients with normal kidney function were similar with a reported median progression-free survival (PFS) of 10.3 months and a median OS of 22.6 months.…”

Retrospective Analysis on Safety and Efficacy of Everolimus in Treatment of Metastatic Renal Cancer Patients Receiving Dialysis

“…The median number of target therapy per patient is 3, with a median duration of treatment of 28 months [19]. Masini et al also reported a multicentric retrospective Italian study evaluating the outcome of patients treated with sunitinib and sorafenib in this setting [20]. The findings agree with each of them showing that tyrosine kinase inhibitors appear to be effective and safe in patients with mRCC and ERSD who were receiving dialysis.…”

The world of targeted therapies in kidney cancers: pitfalls, tips and tricks

“…Studies based on the limited number of patients seem to suggest that concomitant use of sunitinib and dialysis is feasible with good results 19–21. Furthermore, it was suggested that hemodialysis did not significantly alter plasma concentrations of sunitinib 22–24. Although other grade ≥3 toxicities have been reported with concomitant dialysis and sunitinib (mainly hypertension),23,25 we report here, for the first time, related-to-dialysis-and-sun itinib vomiting.…”