The Prognostic Significance of Plasma Interleukin-6 Levels in Patients with Metastatic Hormone-Refractory Prostate Cancer: Results from Cancer and Leukemia Group B 9480

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Abstract
Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)]. Methods: 191 patients entered on CALGB 9480 had pretreatment plasma collected and centrally stored. Using a human IL-6 immunoassay, quantitative levels of IL-6 were measured in duplicate on 300 μL samples. The proportional hazard model was used to assess the prognostic significance of IL-6 in predicting overall survival. Results: Median IL-6 level for the cohort of 191 patients was 4.80 pg/mL. Survival time among patients with IL-6 levels less than or equal to the median was 19 months (95% CI, 17-22) compared with 11 (95% CI, 8-14) months for patients above the median (P = 0.0004). In multivariate analysis, adjusting on performance status, lactate dehydrogenase, and prostate-specific antigen level, the hazard ratio was 1.38 (95% CI, 1.01-1.89; P = 0.043) using the median level as a cut point. Furthermore, a cut point of 13.31 pg/mL revealed robust prognostic significance with a hazard ratio of 2.02 (95% CI, 1.36-2.98; P = 0.0005). Conclusions: Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP.