title: Granulocyte macrophage colony-stimulating factor as a predictor of the response of metastatic renal cell carcinoma to tyrosine kinase inhibitor therapy.
abstract: This prospective study was conducted to identify predictive markers for the response of metastatic renal cell carcinoma (RCC) to tyrosine kinase inhibitors (TKIs). Patients with histologically proven RCC with at least one measurable metastatic lesion were enrolled in this study. Blood samples were collected prior to treatment and the plasma levels of 27 cytokines were measured. Tumor response was assessed 8-12 weeks after the initiation of TKI treatment. A total of 13 patients (11 men and 2 women) with a median age of 63 years received sunitinib (8 cases), sorafenib (1 case), or axitinib (4 cases). Partial response (PR) was achieved in 5 patients (38%), stable disease (SD) in 4 (30%) and progressive disease (PD) was noted in 4 (30%). The plasma granulocyte macrophage colony-stimulating factor (GM-CSF) level in PR cases was significantly higher compared to that in SD or PD cases (P=0.012). Therefore, GM-CSF may be a predictive biomarker of the response of RCC to TKI treatment, suggesting that TKIs may exert clinical effects not only through suppression of the vascular endothelial growth factor, but also through immune system modulation.
authors.affiliation: Department of Urology, Chibanishi General Hospital, Matsudo, Chiba 270-2251, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamada
authors.affiliation: Department of Immunotherapeutics, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Urology, National Center for Global Health and Medicine, Tokyo 162-8655, Japan ; Department of Urology, Tokyo Teisin Hospital, Tokyo 102-8798, Japan.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Immunotherapeutics, University of Tokyo Hospital, Tokyo 113-8655, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
keywords: granulocyte macrophage colony-stimulating factor; metastatic; renal cell carcinoma; tyrosine kinase inhibitors