Combination Of Low-dose Dexamethasone Research Articles

A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse model

BackgroundSjögren syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and diminished secretory function of the salivary glands. Dexamethasone (DEX) resolves dry mouth and lymphocytic infiltration; however, this treatment is difficult to maintain because of multiple adverse effects (eg, osteoporosis and skin thinning); likewise, aspirin-triggered resolvin D1 (AT-RvD1) increases saliva secretion but cannot eliminate lymphocytic infiltration. Previous studies showed that a combination of low-dose DEX with AT-RvD1 before disease onset prevents SS-like features in a mouse model; however, this is not clinically practical because there are no reliable indicators of SS before disease onset. Therefore, the authors applied the combined treatment at disease onset to show its efficacy and comparative lack of adverse effects, so that it may reasonably be maintained over a patient’s lifetime. MethodsNOD/ShiLtJ mice were treated with ethanol (vehicle control), high-dose DEX alone, AT-RvD1 alone, or a combination of low-dose DEX with AT-RvD1 at disease onset for 8 weeks. Then saliva flow rates were measured, and submandibular glands were harvested for histologic analyses. ResultsA combined treatment of low-dose DEX with AT-RvD1 significantly decreased mast cell degranulation and lymphocytic infiltration, increased saliva secretion, and restored apical aquaporin-5 expression in submandibular glands of NOD/ShiLtJ mice. ConclusionsLow-dose DEX combined with AT-RvD1 reduces the severity of SS-like manifestation and prevents the development of advanced and potentially irreversible damage, all in a form that can reasonably be administered indefinitely without the need to cease treatment because of secondary effects.

Combination of Bortezomib, Dexamethasone, Thalidomide and Zoledronic Acid (VdtZ) Results in a High Rate of Complete Response in High-Risk Non-Hodgkin Lymphoma

We previously reported that the combination of low-dose dexamethasone (d) and thalidomide (t) with higher frequency zoledronic acid (ZOMETA, Z) – the “dtZ” regimen – was associated with an overall response rate (RR) of 75.0% in patients with relapsed/refractory multiple myeloma (MM). However, the rate immunofixation (IF)-negative complete reponses (CR) was only 7.7%. In those patients who did not achieve CR, addition of bortezomib (VELCADE, V) to “dtZ” – the “VdtZ” regimen – greatly improved the overall RR to 92.9% and CR to 42.9%. In addition, 21.4% of “dtZ/VdtZ”-treated patients also achieved near-CR (nCR). Amongst 14 consecutive newly-diagnosed patients with MM who were treated with “dtZ/VdtZ”, the RR was 100% and CR/nCR was >75%. Encouraged by these data in MM, we applied the 3-weekly “VdtZ” regimen – intravenous Vel 1.5 mg/m2 days 1, 4, 8 and 11; oral Dex 20 mg days 1, 8 and 15; oral Thal 100 mg days 1–21; and intravenous Zol 4 mg day 1 – in 3 consecutive patients with newly-diagnosed high-risk, difficult-to-treat non-Hodgkin lymphoma (NHL) to determine the feasibility of using “VdtZ” to treat NHL. The patient characteristics and results are summarized in the table below:In summary, all 3 (100%) patients rapidly reported CR upon initiation of “VdtZ. Although significant tumor lysis was reported in all patients, treatment was fairly welltolerated. These data provide a basis for further studies on the “VdtZ” regimen for the treatment of high-risk NHL.ParameterCase 1Case 2Case 3Age, Sex78 years, Male61 years, Female61 years, MaleNHLPTCLDLBCLDLBCLStageIV B E SIV B E SIII B E STumor burdenVery bulkyExtremely bulkyBulkyAdditional featuresPleural effusion, ascitesMassive ascites, pleural effusionSevere autoimmune hemolytic anemiaZubrod score442IPI riskHighHighHighResponse to“VdtZ”CR after 2 cyclesCR after 3 cyclesCR after 1 cycleSurvival to date12 months4 months1 monthPTCL = peripheral T cell lymphoma; DLBCL = diffuse large B cell lymphoma