title: Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer receiving haemodialysis: a retrospective Italian survey.
abstract: 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).
  
  
  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.
authors.affiliation: Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy. cristinamas@libero.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Masini
authors.forename: Roberto
authors.initials: R
authors.lastname: Sabbatini
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Azzurra
authors.initials: A
authors.lastname: Onofri
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Invernizzi
authors.forename: Luca
authors.initials: L
authors.lastname: Moscetti
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Aste
authors.forename: Maria
authors.initials: M
authors.lastname: Pagano
authors.forename: Federica
authors.initials: F
authors.lastname: Grosso
authors.forename: Anna
authors.initials: A
authors.lastname: Lucia Manenti
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ortega
authors.forename: Laura
authors.initials: L
authors.lastname: Cosmai
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D000075202:Contraindications; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000628:therapy; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D006435:Renal Dialysis; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib