title: Baseline chronic kidney disease is associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma.
abstract: To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m. Patients with GFR less than 60 were more likely to encounter severe (grade 3-4) TT-induced toxicities (79 vs. 32%, P<0.0001). Moreover, renal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67-13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.
authors.affiliation: aDepartment of Urology bIRON (equIpe de Recherche Onco-Normande) cDigestive and Urologic Oncology Unit dDepartment of Pathology, Rouen University Hospital eDepartment of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Nouhaud
authors.forename: Christian
authors.initials: C
authors.lastname: Pfister
authors.forename: Guillaume
authors.initials: G
authors.lastname: Defortescu
authors.forename: Anthony
authors.initials: A
authors.lastname: Giwerc
authors.forename: David
authors.initials: D
authors.lastname: Charbit
authors.forename: Sophie
authors.initials: S
authors.lastname: Gouerant
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Di Fiore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007674:Kidney Diseases / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; C401859:temsirolimus; D000077157:Sorafenib; D000077210:Sunitinib; D020123:Sirolimus