Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence.

International audienceInterleukin (IL)-6, a pleiotropic cytokine with varied systemic functions, plays a major role in inflammatory processes. It modulates the transcription of several liver-specific genes during acute inflammatory states, particularly C-reactive protein, and controls the survival of normal plasmablastic cells. In addition, IL-6 has been implicated in hematopoiesis as a cofactor in stem cell amplification and differentiation. This article is the first review of clinical studies in the 1990s with anti-IL-6 monoclonal antibodies (mAbs) in the treatment of patients with cancer and related lymphoproliferative disorders. In six clinical studies of mAbs to IL-6 with BE-8 or CNTO 328 in patients with multiple myeloma, renal cell carcinoma, and B-lymphoproliferative disorders, anti-IL-6 mAb treatment decreased C-reactive protein levels in all patients. In most patients, levels decreased below detectable limits. The antibodies were well tolerated, and no serious adverse effects were observed in the vast majority of studies. The fact that anti-IL-6 mAb therapy decreased the incidence of cancer-related anorexia and cachexia may also be useful in the treatment of cancer patients

The effects of atrasentan on urinary metabolites in patients with type 2 diabetes and nephropathy

We assessed the effect of atrasentan therapy on a pre-specified panel of 13 urinary metabolites known to reflect mitochondrial function in patients with diabetic kidney disease. This post-hoc analysis was performed using urine samples collected during the RADAR study which was a randomized, double-blind, placebo-controlled trial that tested the effects of atrasentan on albuminuria reduction in patients with type 2 diabetes and nephropathy. At baseline, four of the 13 metabolites, quantified by gas-chromatography mass spectrometry, were below detectable levels, and six were reduced in patients with eGFR <60 ml/min/1.73 m(2) . After 12-weeks of atrasentan treatment in patients with eGFR <60 ml/min/1.73 m(2) , a single-value index of the metabolites changed by -0.31 (95%CI -0.60 to -0.02; p = 0.035), -0.08 (-12 to 0.29; p = 0.43) and 0.01 (-0.21 to 0.19; p = 0.913) in placebo, atrasentan 0.75 mg/d and 1.25 mg/d, respectively. The metabolite index difference compared to placebo was 0.13 (-0.17 to 0.43; p = 0.40) and 0.35 (0.05 to 0.65; p = 0.02) for atrasentan 0.75 mg/d and 1.25 mg/d, respectively. These data corroborate previous findings of mitochondrial dysfunction in patients with type 2 diabetes, nephropathy, and eGFR <60 ml/min/1.73 m(2) , suggesting that atrasentan may prevent the progression of mitochondrial dysfunction common to this specific patient population. Future studies of longer treatment duration with atrasentan are indicated