Original articleClinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines
Introduction
Prognostic scores play an important role in the management of patients with metastatic renal cell carcinoma (mRCC). All major randomized trials that established the activity of currently available targeted agents used a prognostic score as one of the principal inclusion or stratification criteria or both. The Memorial Sloan-Kettering Cancer Center (MSKCC) model introduced in 1999 is still widely used with minor modifications [1], [2], [3]. More recently, Heng and collaborators from the International Metastatic Renal-Cell Carcinoma Database Consortium (IDC) developed another prognostic model for patients treated with agents targeting the vascular endothelial growth factor pathway [4]. Prognostic models for mRCC that have been accepted for use in the clinical practice are summarized in Table 1. Although the IDC prognostic model has not been used in any major randomized trial, somewhat controversially it forms the basis for patient stratification in the 2012 European Society for Medical Oncology guidelines for mRCC treatment [5].
The present retrospective study has been designed to test the IDC model in a relatively homogeneous cytokine-pretreated population of patients with mRCC treated with targeted therapies including sunitinib (Pfizer) or sorafenib (Bayer) or both. Cytokines may still represent an option in a subgroup of patients and are used widely in resource-poor medical systems [6]. In addition, patients pretreated with cytokines are routinely analyzed together with those treated with first-line targeted agents in mRCC trials [7], [8].
Section snippets
Patients
Patients treated between June 2007 and April 2012 after progressing on cytokine therapy were included in the present registry-based retrospective analysis. RENIS (RENal Information System, http://renis.registry.cz) is a Czech database of patients with mRCC treated with targeted agents in comprehensive cancer centers [9]. Anonymized entries contain detailed standardized data on baseline characteristics, disease course, and therapy. The data is updated biannually. The registry is estimated to
Baseline characteristics, treatment, and survival
A total of 319 patients treated with sunitinib or sorafenib after progression on cytokines were analyzed, of which 138 received sorafenib, and 181 received sunitinib (Table 2). Out of the 319 patients, 309 (96.9%) patients had clear cell histology, 257 (81.3%) patients had previously received only IFN-α monotherapy, and 281 (88.1%) had undergone prior nephrectomy. As of the date of analysis, 76 (24%) patients were alive and without progression, 27 (8%) patients died before disease progression
Discussion
The present registry-based analysis identified the time from diagnosis to the start of TKI treatment of<1 year, increased ANC, increased LDH, and ECOG PS 2 or higher as independent predictors of OS in patients presenting for second-line TKI therapy. These prognostic parameters overlap to a large extent with the prognostic factors proposed by Heng et al. [4].
Historically, several prognostic systems have been proposed for mRCC, often reflecting the many changes occurring in the treatment
Acknowledgments
We would like to thank the following heads of the comprehensive cancer centers for their permission to use data of patients from their respective regional networks: Professor Jitka Abrahamova, Prague; Dr. Václav Janovský, České Budějovice; Professor Jindřich Fínek, Plzen; Professor Jiří Vorlíček, Brno; Dr. Lubomír Slavíček, Jihlava; Professor Renata Soumarová, Nový Jičín; Dr Jiří Bartoš, Liberec; Dr. David Feltl, Ostrava; Dr. Jana Prausová, Prague; Dr. Milan Lysý, Ústí nad Labem; Dr. Milan
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T.B. has received honoraria for lectures from Bayer and Pfizer. I.K. has participated on advisory board for Bayer. K.K. has received travel grants and lecture fees from Bayer and Pfizer. B.M. has received honoraria for lectures from Bayer.