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The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), which have angiogenic potential and interleukin-6 (IL-6), IL-1beta, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-beta) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-alpha, TGF-beta, IL-1beta did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology.

Introduction: Coronary heart disease (CHD) is the leading cause of death in hemodialysis (HD) patients. Inflammation contributes to the pathogenesis of atherosclerosis in this population. Indoleamine 2,3-dioxygenase (IDO), an enzyme with immunomodulatory properties, was evaluated in HD patients with or without CHD. Methods: Of the total of 66 HD patients, 22 of them with CHD were confirmed by coronary angiography and 24 healthy volunteers were enrolled in the study. Plasma IDO was assessed by means of enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) were also measured. Results: Compared with healthy volunteers, plasma IDO concentration was markedly increased in HD patients (median 8.04 ng/mL vs. 48.9 ng/mL). Serum IL-6 and CRP were also significantly increased in HD patients. Compared with HD patients without CHD, plasma IDO concentration was significantly increased in HD patients with CHD (median 38.6 ng/mL vs. 74.5 ng/mL). Neither IL-6 nor CRP differed between the last two groups. IDO was negatively correlated with IL-6 and CRP. Conclusion: IDO concentration is increased in HD patients and is increased further in HD patients with CHD. It remains to be elucidated if increased IDO plays a direct role in the pathogenesis of atherosclerosis or if it affects atherosclerosis indirectly by curtailing chronic inflammation or both.

BackgroundBevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC). We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.MethodsA total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5) and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group), 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.ResultsOver 4 years of follow-up, there was no statistically significant difference in survival and time to progression between the four treatment groups. After two cycles of chemotherapy, responders and nonresponders were divided according to their response in order to examine the role of initial response as an independent factor in survival and response when a biological agent is combined with chemotherapy. Nonresponders, who received additional therapy with bevacizumab or combination therapy, had a survival benefit [657 days (95% confidence interval 349–970) and 681 days (95% confidence interval 315–912), respectively], which was statistically significant compared with continuation of cytotoxic chemotherapy (P < 0.001). The combination therapy had a safety profile comparable with that of bevacizumab and erlotinib taken individually.ConclusionAdministration of bevacizumab and erlotinib in combination with first-line chemotherapy, followed by bevacizumab and erlotinib monotherapy as maintenance, showed promising results in patients with NSCLC, with reduced toxicity as compared with chemotherapy alone, but did not translate into longer overall survival.

The in vitro inhibition of transforming growth factor alpha and interleukin 8 by paricalcitol confirms the immunomodulatory properties of this vitamin D analogue.