title: Prognostic role of the cumulative toxicity in patients affected by metastatic renal cells carcinoma and treated with first-line tyrosine kinase inhibitors.
abstract: Tyrosine kinase inhibitor-related toxicities have been reported to be predictive and/or prognostic factors in patients affected by metastatic renal cell carcinoma (mRCC). We aim to investigate the incidence of cumulative toxicity and its prognostic role in mRCC patients treated with sunitinib or pazopanib. mRCC patients treated with sunitinib or pazopanib at the European Institute of Oncology in Milan were reviewed for the incidence of adverse events. Cumulative toxicity was defined as the presence of more than one selected adverse event of any grade. Prognoses were evaluated by the International mRCC Database Consortium criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and Cox analysis. A total of 104 patients were included in the final analysis. Only 18.3% did not experience any of the selected toxicities: 26.9% had one, 35.6% had two and 19.2% all three toxicities. Accordingly, 54.8% of patients experienced cumulative toxicity. In those with or without cumulative toxicity, the median PFS was 27.6 versus 7.2 months and the median OS was 61.2 versus 18.7 months, respectively. When cumulative toxicity was adjusted for International mRCC Database Consortium prognostic groups, it maintained its prognostic role for both PFS (hazard ratio: 0.31, 95% confidence interval, 0.20-0.49; P<0.001) and OS (hazard ratio: 0.27, 95% confidence interval, 0.15-0.48; P<0.001). A major limitation was the retrospective and monocentric nature of the analysis. We reported the prognostic role of cumulative toxicity because of hypertension, hypothyroidism and hand-foot syndrome in patients affected by mRCC and treated with sunitinib or pazopanib.
authors.affiliation: aMedical Oncology Division of Urogenital and Head and Neck Tumours, European Institute of Oncology bDivision of Urologic Cancer Surgery, European Institute of Oncology, Milan cMedical Oncology Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.forename: Elena
authors.initials: E
authors.lastname: Verri
authors.forename: Maria
authors.initials: M
authors.lastname: Cossu Rocca
authors.forename: Gaetano
authors.initials: G
authors.lastname: Aurilio
authors.forename: Daniela
authors.initials: D
authors.lastname: Cullurà
authors.forename: Ottavio
authors.initials: O
authors.lastname: de Cobelli
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D007191:Indazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D000077210:Sunitinib