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

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 ML 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.

Serum Levels of Trace Elements in Patients with Prostate Cancer

“…Interleukin-6 (IL-6)-hepcidin axis that regulates iron metabolism is one of the mechanisms which explain our finding of low iron levels in patients with poorer prognosis. Prostate cancer patients with poorer prognosis have higher circulating IL-6 levels (Michalaki et al, 2004;George et al, 2005). It is known that the cytokine leads hepcidin generation in liver (Ganz, 2006).…”

Growth differentiation factor-15 upregulates interleukin-6 to promote tumorigenesis of prostate carcinoma PC-3 cells

“…Prolonged treatment with IL6 results in generations of sublines that express a more malignant prostate phenotype (Culig 2011). Previous studies have shown that plasma IL6 levels have prognostic significance in patients with metastatic hormone-refractory prostate cancer (George et al 2005). An increase in serum cytokines including IL6 was found in cachectic patients with prostate carcinoma, and immunostaining levels of IL6 and its receptor increased with Gleason score (Pfitzenmaier et al 2003, Royuela et al 2004.…”

Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer

“…Lactate dehydrogenase levels may be a marker for tumour burden (Smaletz et al, 2002;George et al, 2005). It was observed that patients experienced a decrease in their LDH levels during treatment.…”