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.
Written by:
Masini C, Sabbatini R, Porta C, Procopio G, Di Lorenzo G, Onofri A, Buti S, Iacovelli R, Invernizzi R, Moscetti L, Aste MG, Pagano M, Grosso F, Lucia Manenti A, Ortega C, Cosmai L, Del Giovane C, Conte PF. Are you the author?
Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena; Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia; Department of Medical Oncology, Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Department of Endocrinology and Medical Oncology, Genitourinary Cancer Section, University Federico II, Naples; Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche, Ancona; Department of Oncology, Azienda Istituti Ospitalieri di Cremona, Cremona; Department of Radiology, Oncology and Human Pathology, Sapienza University, Rome; Medical Oncology, Busto Arsizio, Varese; Department of Medical Oncology, Central Hospital of Belcolle, Viterbo; Department of Oncology, Haematology, UOC of Oncology, Ospedale Businco, ASL 8, Cagliari; Department of Medical Oncology, Arcispedale Santa Maria Nuova, Reggio Emilia Medical Oncology, Ospedale SS Antonio e Biagio, Alessandria; Oncology DH, Ospedale C. Magati, Scandiano Gruppo Italiano Oncologia Nefrologica (GION), Pavia, Via Liutprando 9 Oncologia Medica a Direzione Universitaria, Fondazione del Piemonte per l'Oncologia, Istituto per la Ricerca e Cura del Cancro Candiolo Torino U.O. Nefrologia e Dialisi, Azienda Istituti Ospitalieri di Cremona, Italy.
Reference: BJU Int. 2012 Feb 24. Epub ahead of print.
doi: 10.1111/j.1464-410X.2012.10946.x
PubMed Abstract
PMID: 22364110
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